Aryl and heteroarylcyclopropyl oxime ethers and their use as fungicides

ABSTRACT

Compounds with fungicidal and insecticidal properties having formula                    
     wherein X is N or CH; Z is O, S or NR 8 ; A is hydrogen, halo, cyano, (C 1 -C 12 )alkyl, or (C 1 -C 12 )alkoxy; R 1  and R 8  are independently hydrogen or (C 1 -C 4 )alkyl; R 2  is hydrogen, (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, (C 3 -C 7 )cycloalkyl, halo(C 3 -C 7 )cycloalkyl, (C 2 -C 8 )alkenyl, halo(C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, halo(C 2 -C 8 )alkynyl, aryl, aralkyl, heterocyclic, heterocyclic(C 1 -C 4 )alkyl or C(R 10 )═N—OR 9 ; R 3  is hydrogen, (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, (C 3 -C 7 )cycloalkyl, halo(C 3 -C 7 )cycloalkyl, (C 2 -C 8 )alkenyl, halo(C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, halo(C 2 -C 8 )alkynyl, aryl, aralkyl, aryl(C 3 -C 7 )cycloalkyl, heterocyclic or heterocyclic(C 1 -C 4 )alkyl; R 4  and R 5  are independently hydrogen, (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, (C 3 -C 7 )cycloalkyl, halo(C 3 -C 7 )cycloalkyl, (C 2 -C 8 )alkenyl, halo(C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, halo(C 2 -C 8 )alkynyl, halo, cyano, (C 1 -C 4 )alkoxycarbonyl, aryl, aralkyl, aryl(C 3 -C 7 )cycloalkyl, heterocyclic or heterocyclic(C 1 -C 4 )alkyl; R 6  is hydrogen, (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, (C 3 -C 7 )cycloalkyl, halo(C 3 -C 7 )cycloalkyl, (C 2 -C 8 )alkenyl, halo(C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, halo(C 2 -C 8 )alkynyl, halo, cyano, (C 1 -C 4 )alkoxycarbonyl, aryl, aralkyl, aryl(C 3 -C 7 )cycloalkyl, heterocyclic or heterocyclic(C 1 -C 4 )alkyl; R 7  is aryl, aralkyl, heterocyclic or heterocyclic(C 1 -C 4 )alkyl; R 9  is hydrogen, (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, (C 2 -C 8 )alkenyl, halo(C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, halo(C 2 -C 8 )alkynyl, (C 1 -C 4 )alkylcarbonyl, (C 1 -C 4 )alkoxycarbonyl, aryl, or aralkyl; and R 10  is hydrogen, (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, (C 3 -C 7 )cycloalkyl, halo(C 3 -C 7 )cycloalkyl, (C 2 -C 8 )alkenyl, halo(C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, halo(C 2 -C 8 )alkynyl, aryl, aralkyl, heterocyclic, or heterocyclic(C 1 -C 4 )alkyl.

This application is a CIP of 09/238,196, filed Jan. 27, 1999, now U.S.Pat. No. 6,063,956.

The present invention relates to certain aryl cyclopropyl oxime ethercompounds, compositions containing these compounds, and methods forcontrolling fungi by the use of a fungitoxic amount of these compounds.

Compounds having certain oxime ether structures are disclosed in U.S.Pat. Nos. 5,194,662 and 5,292,759. We have discovered a group ofcyclopropyl oxime ethers which possess a substituted aryl andheterocyclic moieties which possess broad spectrum fungicidalproperties.

The cyclopropyloxime ethers of the present invention have the Formula(I)

wherein X is N or CH; Z is O, S, or NR₈;

A is hydrogen, halo, cyano, (C₁-C₁₂)alkyl, or (C₁-C₁₂)alkoxy;

R₁ and R₈ are independently hydrogen or (C₁-C₄)alkyl;

R₂ is hydrogen, (C₁-C₁₂)alkyl, halo(C₁-C₁₂)alkyl, (C₃-C₇)cycloalkyl,halo(C₃-C₇)cycloalkyl, (C₂-C₈)alkenyl, halo(C₂-C₈)alkenyl,(C₂-C₈)alkynyl, halo(C₂-C₈)alkynyl, or cyano;

R₃ is hydrogen, (C₁-C₁₂)alkyl, halo(C₁-C₁₂)alkyl, (C₃-C₇)cycloalkyl,halo(C₃-C₇)cycloalkyl, (C₂-C₈)alkenyl, halo(C₂-C₈)alkenyl,(C₂-C₈)alkynyl, or halo(C₂-C₈)alkynyl;

R₄ and R₅ are independently hydrogen, (C₁-C₁₂)alkyl, halo(C₁-C₁₂)alkyl,(C₃-C₇)cycloalkyl, halo(C₃-C₇)cycloalkyl, (C₂-C₈)alkenyl,halo(C₂-C₈)alkenyl, (C₂-C₈)alkynyl, halo(C₂-C₈)alkynyl, halo, cyano, or(C₁-C₄)alkoxycarbonyl; and wherein

A) R₇ is aryl, arylalkyl, heterocyclic or heterocyclic(C₁-C₄)alkylwherein the aryl or heterocyclic ring is substituted with from 2 to 5substituents and wherein the positions on the aryl or heterocyclic ringadjacent to the bond to the cyclopropyl ring are both substituted and R₆is hydrogen, (C₁-C₁₂)alkyl, halo(C₁-C₁₂)alkyl, (C₃-C₇)cycloalkyl,halo(C₃-C₇)cycloalkyl, (C₂-C₈)alkenyl, halo(C₂-C₈)alkenyl,(C₂-C₈)alkynyl, or halo(C₂-C₈)alkynyl; or

B) R₇ is aryl, arylalkyl, heterocyclic or heterocyclic(C₁-C₄)alkylwherein the aryl or heterocyclic ring is unsubstituted or substitutedfrom 1 to 4 substituents wherein at least one of the positions on thearyl or heterocyclic ring adjacent to the bond to the cyclopropyl ringis a hydrogen and R₆ is (C₁-C₁₂)alkyl, halo(C₁-C₁₂)alkyl,(C₃-C₇)cycloalkyl, halo(C₃-C₇)cycloalkyl, (C₂-C₈)alkenyl,halo(C₂-₈)alkenyl, (C₂-C₈)alkynyl, or halo(C₂-C₈)alkynyl; and theirsalts, complexes, enantiomorphs, and stereoisomers; and mixturesthereof.

The aforementioned (C₁-C₁₂)alkyl, (C₂-C₈)alkenyl, (C₂-C₈)alkynyl and(C₃-C₇)cycloalkyl groups may be optionally and independently substitutedwith up to three substituents selected from nitro, halomethyl,(C₁-C₄)alkoxycarbonyl, and cyano.

The term alkyl includes both branched and straight chain alkyl groupsfrom 1 to 12 carbon atoms. Typical alkyl groups are methyl, ethyl,n-propyl, iso-propyl, n-butyl, sec-butyl, isobutyl, t-butyl, n-pentyl,isopentyl, n-hexyl, n-heptyl, isooctyl, nonyl, decyl, undecyl, dodecyland the like. The term haloalkyl refers to an alkyl group substitutedwith from 1 to 3 halogens.

The term alkenyl refers to an ethylenically unsaturated hydrocarbongroup, straight or branched, having a chain length of from 2 to 8 carbonatoms and 1 or 2 ethylenic bonds. The term haloalkenyl refers to analkenyl group substituted with from 1 to 3 halogen atoms. The termalkynyl refers to an unsaturated hydrocarbon group, straight orbranched, having a chain length of from 2 to 8 carbon atoms and 1 or 2acetylenic bonds.

The term aryl includes phenyl and naphthyl which maybe substituted withup to four substituents independently selected from halogen, cyano,nitro, trihalomethyl, trihalomethoxy, phenyl, phenoxy, (C₁-C₄)alkyl,(C₃-C₇)cycloalkyl, (C₂-C₈)alkenyl, (C₁-C₄)alkoxy, (C₁-C₄)alkylthio,(C₁-C₄)alkylsulfoxide, halo(C₁-C₄)alkyl, halo(C₁-C₄)alkoxy,halo(C₃-C₇)cycloalkyl, halo(C₂-C₈)alkenyl, or (C₁-C₄)alkoxycarbonyl.Typical phenyl substituents, wherein at least one of the positions onthe phenyl ring adjacent to the bond to the cyclopropyl ring issubstituted with hydrogen include but are not limited to 2-chloro,3-chloro, 4-chloro, 2-fluoro, 3-fluoro, 4-fluoro, 2-bromo, 3-bromo,4-bromo, 2-methyl, 3-methyl, 4-methyl, 2-trifluoromethyl,3-trifluoromethyl, 4-trifluoromethyl, 2-methoxy, 3-methoxy, 4-methoxy,2-trifluoromethoxy, 3-trifluoromethoxy, 4-trifluoromethoxy, 2-cyano,3-cyano, 4-cyano, 2,3-dichloro, 2,3-difluoro, 2,3-dibromo, 2,3-dimethyl,2,3-dimethoxy, 2,3-bis(trifluoromethyl), 2,3bis-(trifluoromethoxy),2,4-difluoro, 2,4-dichloro, 2,4-dibromo, 2,4-dimethyl, 2,4-dimethoxy,2,4-bis(trifluoromethyl), 2,4-bis(trifluoromethoxy), 2,5-difluoro,2,5-dichloro, 2,5-dibromo, 2,5-dimethyl, 2,5-dimethoxy,2,5-bis(trifluoromethyl), 2,5-bis-(trifluoromethoxy), 3,4-difluoro,3,4-dichloro, 3,4-dibromo, 3,4-dimethyl, 3,4-dimethoxy,3,4-bis(trifluoromethyl), 3,4-bis(trifluoromethoxy), 3,5-difluoro,3,5-dichloro, 3,5-dibromo, 3,5-dimethyl, 3,5-bis(trifluoromethyl),3,5-bis(trifluoromethoxy), 2,3,4-trifluoro, 2,3,4-trichloro,2,3,4-tribromo, 2,3,4-trimethyl, 2,3,4-trimethoxy,2,3,4-tris(trifluoromethyl), 2,3,4-tris(trifluoromethoxy),2,3,5-trifluoro, 2,3,5-trichloro, 2,3,5-tribromo, 2,3,5-trimethyl,2,3,5-tris(trifluoromethyl), 2,3,5-tris(trifluoromethoxy),2,4,5-trifluoro, 2,4,5-trichloro, 2,4,5-tribromo, 2,4,5-trimethyl,2,4,5-trimethoxy, 2,4,5-tris(trifluoromethyl),2,4,5-tris(trifluoromethoxy), 3,4,5-trifluoro, 3,4,5-trichloro,3,4,5-tribromo, 3,4,5-trimethyl, 3,4,5-trimethoxy,3,4,5-tris(trifluoromethyl), 3,4,5-tris(trifluoromethoxy),2,3,4,5-tetrafluoro, 2,3,4,5-tetrachloro, 2,3,4,5-tetrabromo,2,3,4,5-tetramethyl, 2,3,4,5-tetramethoxy,2,3,4,5-tetra(trifluoromethyl), and 2,3,4,5-tetra(tetrafluoromethoxy.

Typical phenyl substituents, where both positions on the phenyl ringadjacent to the bond to the cyclopropyl rings are substituted includebut are not limited to 2,6-dichloro, 2,3,6-trichloro, 2,4,6-trichloro,2,6-difluoro, 2,3,6-trifluoro, 2,4,6-trifluoro, 2,6-dibromo,2,3,6-tribromo, 2,4,6-tribromo 2,3,4,6-tetrachloro, 2,3,5,6-tetrachloro,2,3,4,5,6-pentachloro, 2,3,4,6-tetrabromo, 2,3,5,6-tetrabromo,2,3,4,5,6-pentabromo, 2,3,4,6-tetrafluoro, 2,3,5,6-tetrafluoro,2,3,4,5,6-pentafluoro, 2,6-dimethyl, 2,3,6-trimethyl, 2,4,6-trimethyl,2,6-dimethoxy, 2,3,6-trimethoxy, 2,4,6-trimethoxy, 2,6-diethoxy,2,3,6-triethoxy, 2,4,6-triethoxy, 2,3,4,6-tetramethyl,2,3,5,6-tetramethyl, 2,3,4,5,6-pentamethyl, 2,3,4,6-tetramethoxy,2,3,5,6-tetramethoxy, 2,3,4,5,6-pentamethoxy, 2,3,4,6-tetraethoxy,2,3,5,6-tetraethoxy, 2,3,4,5,6-pentaethoxy, 2,6-dicyano, 2,3,6-tricyano,2,4,6-tricyano, 2,6-dinitro, 2,6-diphenyl, 2,6-diphenoxy, 2,6-dibenzyl,2,6-bis(trifluoromethyl), 2,3,6-tris(trifluoromethyl),2,4,6-tris-(trifluoromethyl), 2,3,4,6-tetra(trifluoromethyl),2,3,5,6-tetra(trifluoromethyl), 2,3,4,5,6-penta(trifluoromethyl),2,6-bis-(trifluoromethoxy), 2,3,6-tris(trifluoromethoxy),2,4,6-tris(trifluoromethoxy), 2,3,4,5-tetra(trifluoromethoxy),2,3,4,6-tetra-(trifluoromethoxy), 2,3,5,6-tetra(trifluoromethoxy),2,3,4,5,6-penta(trifluoromethoxy), 2-bromo-6-chloro, 2-bromo-6-fluoro,2-bromo-6-(trifluoromethyl), 2-bromo-6-methyl, 2-bromo-6-methoxy,2-bromo-6-(trifluoromethoxy), 2-bromo-6-cyano, 2-chloro-6-fluoro,2-chloro-6-(trifluoromethyl), 2-chloro-6-methyl, 2-chloro-6-methoxy,2-chloro-6-trifluoromethoxy), 2-chloro-6-cyano,2-fluoro-6-(trifluoromethyl), 2-fluoro-6-methyl, 2-fluoro-6-methoxy,2-fluoro-6-(trifluoromethoxy), 6-cyano-2-fluoro,2-methyl-6-(trifluoromethyl), 6-methoxy-2-methyl,2-methyl-6-(trifluoromethoxy), 6-cyano-2-methyl, 3,6-dichoro-2-fluoro,3-chloro-2,6-difluoro, 4-chloro-2,6-difluoro, 2-bromo-3,6-dichoro,2,3-dibromo-6-chloro, 3-chloro-2,6-dibromo, 2,6-dichloro-3-fluoro,2,3-dichloro-6-fluoro, 2-chloro-3,6-difluoro, 3-bromo-2,6-dichloro,3-bromo-2,6-fluoro, 3-bromo-6-chloro-2-fluoro,2-bromo-5-chloro-6-fluoro, 2,6-dibromo-3-fluoro, 2,5-dibromo-6-fluoro,2,4-dichloro-6-fluoro, 2,6-chloro-4-fluoro, 2,4,-dichloro-6-bromo,2,6-dichloro-4-bromo, 2,4-difluoro-6-chloro, 2,4-difluoro-6-bromo,2,6-difluoro-4-bromo, 2,4-dibromo-6-fluoro, 2,4-dibromo-6-chloro,2,6-dibromo-4-chloro, 2,6-dibromo-4-fluoro, 2,4-dichloro-6-methyl,2,6-dichloro-4-methyl, 2-chloro-4,6-dimethyl, 4-chloro-2,6-dimethyl,2,4-difluoro-6-methyl, 2,6-difluoro-4-methyl, 2-fluoro-4,6-dimethyl,4-fluoro-2,6-dimethyl, 2,4-dibromo-6-methyl, 2,6-dibromo-4-methyl,2-bromo-4,6-dimethyl, 4-bromo-2,6-dimethyl, 2,4-dichloro-6-methoxy,2,6-dichloro-4-methoxy, 2-chloro-4,6-dimethoxy, 4-chloro-2,6-dimethoxy,2,4-difluoro-6-methoxy, 2,6-difluoro-4-methoxy-, 2-fluoro-4,6-dimethoxy,4-fluoro-2,6-dimethoxy, 2,4-dibromo-6-methoxy, 2,6-dibromo-4-methoxy,4-bromo-2,6-dimethoxy, 4-bromo-2,6-dimethoxy,2,4-dichloro-6-(trifluoromethyl), 2,6-dichloro-4-(trifluoromethyl),2-chloro-4,6-bis(trifluoromethyl), 4-chloro-2,6-bis(trifluoromethyl),2,4-difluoro-6-(trifluoromethyl), 2,6-difluoro-4-(trifluoromethyl),2-fluoro-4,6-bis(trifluoromethyl), 4-fluoro-2,6-bis(trifluoromethyl),2,4-dibromo-6-(trifluoromethyl), 2,6-dibromo-4-(trifluoromethyl),2-bromo-4,6-bis(trifluoromethyl), 4-bromo-2,6-bis(trifluoromethyl),2-chloro-4,6-bis(trifluoromethoxy), 4-chloro-2,6-bis(trifluoromethoxy),2,4-difluoro-6-(trifluoromethoxy), 2,6-difluoro-4-(trifluoromethoxy),2-fluoro-4,6-bis(trifluoromethoxy), 4-fluoro-2,6-bis(trifluoromethoxy),2,4-dibromo-6-(trifluoromethoxy), 2,6-dibromo-4-(trifluoromethoxy),2-bromo-4,6-bis(trifluoromethoxy), 4-bromo-2,6-bis(trifluoromethoxy),4,6-dichloro-2-nitro, 4,6-dibromo-2-nitro, 4,6-difluoro-2-nitro,2,6-dichloro-4-nitro, 2-bromo-3,4,6-trichloro, 6-fluoro-2,4,5-trichloro,6-chloro-2,4,5-tribromo, 6-fluoro-2,4,5-tribromo,2-bromo-3,4,6-trifluoro, 2-chloro-3,4,6-trifluoro,6-methyl-2,4,5-trichloro, 6-methyl-2,4,5-tribromo,6-methyl-3,4,6-trifluoro, 6-(trifluoromethyl)-2,4,5-trichloro,6-(trifluoromethyl)-2,4,5-tribromo, 2-(trifluoromethyl)-3,4,6-trifluoro,6-(trifluoromethoxy)-2,4,5-tribromo,2-(trifluoromethoxy)-3,4,6-trifluoro,6-(trifluoromethoxy)-2,4,5-trichloro, 2-bromo-3,5,6-trichloro,6-fluoro-2,3,5-trichloro, 6-chloro-2,3,5-tribromo,6-fluoro-2,3,5-tribromo, 2-bromo-3,5,6-trifluoro,2-chloro-3,5,6-trifluoro, 6-methyl-2,3,5-trichloro,6-methyl-2,3,5-tribromo, 2-methyl-3,5,6-trifluoro,6-(trifluoromethyl)-2,3,5-trichloro, 6-(trifluoromethyl)-2,3,5-tribromo,2-(trifluoromethyl)-3,5,6-trifluoro,2-(trifluoromethoxy)-3,5,6-trichloro,6-(trifluoromethoxy)-2,3,5-tribromo,2-(trifluoromethoxy)-3,5,6-trifluoro, 4-bromo-2,3,5,6-tetrachloro,4-fluoro-2,3,5,6-tetrachloro,4-chloro-2,3,5,6-tetrabromo-,4-fluoro-2,3,5,6-tetrabromo, 4-chloro-2,3,5,6-tetrafluoro,4-bromo-2,3,5,6-tetrafluoro, 2-bromo-3,4,5,6-tetrachloro,6-fluoro-2,3,4,5-tetrachloro-, 2-chloro-3,4,5,6-tetrafluoro,2-bromo-3,4,5,6-tetrafluoro, 2-chloro-3,4,5,6-tetrabromo,2-fluoro-3,4,5,6-tetrabromo, 4-methyl-2,3,5,6-tetrachloro,4-methyl-2,3,5,6-tetrabromo, 4-methyl-2,3,5,6-tetrafluoro,2,3,5,6-tetrachloro-4-(trifluoromethyl),2,3,5,6-tetrabromo-4-(trifluoromethyl),2,3,5,6-tetrafluoro-4-(trifluoromethyl),2,3,5,6-tetrachloro-4-(trifluoromethoxy),2,3,5,6-tetrabromo-4-(trifluoromethoxy,2,3,5,6-tetrafluoro-4-(trifluoromethoxy), 6-methyl-2,3,4,5-tetrachloro,6-methyl-2,3,4,5-tetrabromo, 2-methyl-3,4,5,6-tetrafluoro,2,3,4,5-tetrachloro-6-(trifluoromethyl),2,3,4,5-tetrabromo-6-(trifluoromethyl),3,4,5,6-tetrafluoro-2-(trifluoromethyl),2,3,4,5-tetrachloro-6-(trifluoromethoxy),2,3,4,5-tetrabromo-6-(trifluoromethoxy), and3,4,5,6-tetrafluoro2-(trifluoromethoxy).

The term heterocyclic refers to a substituted 6 membered unsaturatedring selected from 3- or 4-pyridinyl, 5-pyrimidinyl, 3-pyridazinyl or a5 membered unsaturated ring selected from 3-thienyl, 3-furyl,3-pyrrolyl, 4-isoxazolyl, 4-isothiazolyl or 4-pyrazolyl wherein both thepositions on the heterocyclic ring adjacent to the bond to thecyclopropyl ring are substituted and the ring is substituted with from 2to 4 substituents independently selected from (C₁-C₄) alkyl,(C₃-C₇)cycloalkyl, trihalomethyl, trihalomethoxy, halogen, cyano,(C₁-C₄)alkoxycarbonyl, nitro, phenyl, and phenoxy. The term heterocyclicalso refers to a substituted or unsubstituted 6 membered unsaturatedring containing one, two or three heteroatoms, preferably one, two orthree heteroatoms independently selected from oxygen, nitrogen, andsulfur or a 5 membered unsaturated ring containing one, two or threeheteroatoms, preferably one or two heteroatoms independently selectedfrom oxygen, nitrogen, and sulfur wherein the heterocyclic ring isunsubstituted or is substituted with from 1 to 3 substituents wherein atleast one of the positions of the heterocyclic ring adjacent to the bondto the cyclopropyl ring is a hydrogen substituent. Examples ofheterocycles include but are not limited to 2-, 3- or 4-pyridinyl,pyrazinyl, 4-, or 5-pyrimidinyl, pyridazinyl, pyrazole, imidazolyl, 2 or3-thienyl, 2 or 3-furyl, 3-pyrrolyl, oxazolyl, isoxazolyl, thiazolyl,isothiazolyl, oxadiazolyl, and thiadiazolyl. These rings may beoptionally substituted with up from 1 to 3 substituents independentlyselected from (C₁-C₄) alkyl, (C₃-C₇)cycloalkyl, trihalomethyl, halogen,cyano, (C₁-C₄)alkoxycarbonyl, nitro, phenyl, and phenoxy.

The term arylalkyl is used to describe a group wherein the alkyl chainis from 1 to 10 carbon atoms and can be branched or straight chain,preferably a straight chain, with the aryl portion, as defined above,forming a terminal portion of the arylalkyl moiety. Typical arylalkylmoieties are optionally substituted benzyl, phenethyl, phenpropyl, andphenbutyl moieties.

Typical benzyl moieties wherein at least one of the positions on thephenyl ring, adjacent to the methylene which is bonded to thecyclopropyl ring, is substituted with hydrogen include but are notlimited to 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl,2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2-bromobenzyl,3-bromobenzyl, 4-bromobenzyl, 2-trifluoromethylbenzyl,3-trifluoromethylbenzyl, 4-trifluoromethylbenzyl, 2-methylbenzyl,3-methylbenzyl, 4-methylbenzyl 2,3-difluorobenzyl, 2,3-dichlorobenzyl,2,3-dibromobenzyl, 2,3-dimethylbenzyl, 2,4-difluorobenzyl,2,4-dichlorobenzyl, 2,4-dibromobenzyl, 2,4-dimethylbenzyl,2,5-difluorobenzyl, 2,5-dichlorobenzyl, 2,5-dibromobenzyl,2,5-dimethylbenzyl, 3,4-difluorobenzyl, 3,4-dichlorobenzyl,3,4-dibromobenzyl, 3,4-dimethylbenzyl, 3,5-difluorobenzyl,3,5-dichlorobenzyl, 3,5-dibromobenzyl, 3,5-dimethylbenzyl,2,3,4-triifluorobenzyl, 2,3,4-trichlorobenzyl, 2,3,4-tribromobenzyl, and3,4,5-trichlorobenzyl.

Typical benzyl moieties wherein both positions on the phenyl ring,adjacent to the methylene which is bonded to the cyclopropyl ring, aresubstituted include but are not limited to 2,6-dichlorobenzyl,2,3,6-trichlorobenzyl, ]2,4,6-trichlorobenzyl, 2,6-difluorobenzyl,2,3,6-fluorobenzyl, 2,4,6-trifluorobenzyl,2,6-bis(trifluoromethyl)benzyl, 2,3,6-tris(trifluoromethyl)benzyl,2,4,6-tris(trifluoromethyl)benzyl, 2,3,4,6-tetrachlorobenzyl,2,3,5,6-tetrachlorobenzyl, 2,3,4,5,6-pentachlorobenzyl,2,3,4,6-tetrabromobenzyl, 2,3,5,6-tetrabromobenzyl,2,3,4,5,6-pentabromobenzyl, 2,3,4,6-tetrafluorobenzyl,2,3,5,6-tetrafluorobenzyl, and 2,3,4,5,6-pentafluorobenzyl. Typicalphenethyl moieties wherein at least one of the positions on the phenylring, adjacent to the ethyl moiety which is bonded to the cyclopropylring, is substituted with hydrogen include but are not limited to2-(2-chlorophenyl)ethyl, 2-(3-chlorophenyl)ethyl,2-(4-chlorophenyl)ethyl, 2-(2-fluorophenyl)ethyl,2-(3-fluorophenyl)ethyl, 2-(4-fluorophenyl)ethyl,2-(2-methylphenyl)ethyl, 2-(3-methylphenyl)ethyl,2-(4-methylphenyl)ethyl, 2-(4-trifluoromethylphenyl)ethyl,2-(2,4-dichlorophenyl)ethyl, and 2-(3,5-dimethoxyphenyl)ethyl. Typicalphenethyl moieties wherein both positions on the phenyl ring, adjacentto the ethyl moiety which is bonded to the cyclopropyl ring, aresubstituted include but are not limited to 2-(2,6-dichlorophenyl)ethyl,2-(2,3,6-trichlorophenyl)ethyl, 2-(2,4,6-trichlorophenyl)ethyl,2-(2,6-difluorophenyl)ethyl, 2-(2,3,6-trifluorophenyl)ethyl,2-(2,4,6-trifluorophenyl)ethyl, 2-(2,6-dimethylphenyl)ethyl,2-(2,3,6-trimethylphenyl)ethyl, 2-(2,4,6-trimethylphenyl)ethyl,2-(2,6-bis(trifluoromethyl)phenyl)ethyl,2-(2,3,6-tris(trifluoromethyl)phenyl)ethyl,2-(2,4,6-tris(trifluoromethyl)phenyl)ethyl,2-(2,6-dimethoxyphenyl)ethyl, 2-(2,3,6-trimethoxyphenyl)ethyl, and2-(2,4,6-trimethoxyphenyl)ethyl. Typical phenpropyl moieties wherein atleast one of the positions on the phenyl ring, adjacent to the propylmoiety which is bonded to the cyclopropyl ring, is substituted withhydrogen include but are not limited to 3-phenylpropyl,3-(2-chlorophenyl)propyl, 3-(3-chlorophenyl)propyl,3-(4-chlorophenyl)propyl, 3-(2,4-dichlorophenyl)propyl,3-(2-fluorophenyl)propyl, 3-(3-fluorophenyl)propyl,3-(4-fluorophenyl)propyl, 3-(2-methylphenyl)propyl,3-(3-methylphenyl)propyl, 3-(4-methylphenyl)propyl,3-(4-trifluoromethylphenyl)propyl, 3-(2,4-dichlorophenyl)propyl, and3-(3,5-dimethylphenyl)propyl. Typical phenpropyl moieties wherein bothpositions on the phenyl ring, adjacent to the propyl moiety which isbonded to the cyclopropyl ring, are substituted include but are notlimited to 3-(2,6-dichlorophenyl)propyl,3-(2,3,6-trichlorophenyl)propyl, 3-(2,4,6-trichlorophenyl)propyl,3-(2,6-difluorophenyl)propyl, 3-(2,3,6-trifluorophenyl)propyl,3-(2,4,6-trifluorophenyl)propyl, 3-(2,6-dimethylphenyl)propyl,3-(2,3,6-trimethyl-phenyl)propyl, 3-(2,4,6-trimethylphenyl)propyl and3-(2,6-bis(trifluoromethyl)phenyl)propyl. Typical phenbutyl moietieswherein at least one of the positions on the phenyl ring, adjacent tothe butyl moiety which is bonded to the cyclopropyl ring, is substitutedwith hydrogen include but are not limited to 4-phenylbutyl,4-(2-chlorophenyl)butyl, 4-(3-chlorophenyl)butyl,4-(4-chlorophenyl)butyl, 4-(2-fluorophenyl)butyl,4-(3-fluorophenyl)butyl, 4-(4-fluorophenyl)butyl,4-(2-methylphenyl)butyl, 4-(3-methylphenyl)butyl,4-(4-methylphenyl)butyl and 4-(2,4-dichlorophenyl)butyl. Typicalphenbutyl moieties wherein both positions on the phenyl ring, adjacentto the butyl moiety which is bonded to the cyclopropyl ring, aresubstituted include but are not limited to 4-(2,6-di-chlorophenyl)butyl,4-(2,3,6-trichlorophenyl)butyl, 4-(2,4,6-trichlorophenyl)butyl,4-(2,6-difluorophenyl)butyl, 4-(2,3,6-trifluorophenyl)butyl,4-(2,4,6-trifluorophenyl)butyl, 4-(2,6-dimethylphenyl)butyl,4-(2,3,6-trimethylphenyl)butyl, 4-(2,4,6-trimethylphenyl)butyl and4-(2,6-bis(trifluoromethyl)phenyl)butyl.

Halogen or halo includes iodo, fluoro, bromo and chloro moieties.

The compounds of the general Formula I may be obtained in preparation asE/Z isomeric mixtures. These isomers can be separated into individualcomponents by conventional means. The substituted cyclopropanes ofFormula I may be obtained in preparation as cis and trans isomericmixtures which can be separated into individual components byconventional means. Both the individual isomeric compounds and mixturesthereof form subjects of the invention and can be used as fungicides andinsecticides.

One preferred embodiment of this invention is the compounds,enantiomorphs, salts and complexes of Formula I wherein X is CH or N; Zis O or NH; A=R₃=R₄=R₅=hydrogen; R₁ and R₂ are CH₃; R₇ is2,6-dichlorophenyl or 2,6-difluorophenyl; and R₆ is hydrogen.

Another preferred embodiment of this invention is the compounds,enantiomorphs, salts and complexes of Formula I wherein X is CH or N; Zis O or NH; A=R₃=R₄=R₅=hydrogen; R₁ and R₂ are CH₃; R₇ is2,6-dichlorophenyl or 2,6-difluorophenyl; and R₆ is (C₁-C₁₂)alkyl,halo(C₁-C₁₂)alkyl, (C₃-C₇)cycloalkyl, halo(C₃-C₇)cycloalkyl,(C₂-C₈)alkenyl, halo(C₂-C₈)alkenyl, (C₂-C₈)alkynyl, orhalo(C₂-C₈)alkynyl.

A more preferred embodiment of this invention is the compounds,enantiomorphs, salts and complexes of Formula I wherein X is CH or N; Zis O or NH; A is hydrogen; R₁ and R₂ are independently (C₁-C₄)alkyl; R₃,R₄, and R₅ are hydrogen; R₇ is phenyl other than 2,6-dichlorophenyl or2,6-difluorophenyl such that the positions on the phenyl ring adjacentto the bond to the cyclopropyl rings are substituted, and R₆ is selectedfrom hydrogen, (C₁-C₁₂)alkyl, halo(C₁-C₁₂)alkyl, (C₃-C₇)cycloalkyl,halo(C₃-C₇)cycloalkyl, (C₂-C₈)alkenyl, halo(C₂-C₈)alkenyl,(C₂-C₈)alkynyl, and halo(C₂-C₈)alkynyl.

Another more preferred embodiment of this invention is the compounds,enantiomorphs, salts and complexes of Formula I wherein X is CH or N; Zis O or NH; A is hydrogen; R₁ and R₂ are independently (C₁-C₄)alkyl; R₃,R₄ and R₅ are hydrogen; R₆ is hydrogen or (C₁-C₁₂)alkyl; and R₇ is2,3,6-trisubstitutedphenyl, 2,4,6-trisubstitutedphenyl,2,3,4,6-tetrasubstitutedphenyl, 2,3,5,6-tetrasubstituted, or2,3,4,5,6-pentasubstitutedphenyl.

An even more preferred embodiment of this invention are the compounds,enantiomorphs, salts and complexes of Formula I wherein X is N; Z is NH;A is hydrogen; R₁ and R₂ is CH₃; R₃, R₄ and R₅ are hydrogen; R₆ ishydrogen or (C₁-C₄)alkyl; and R₇ is 2,3,6-trihalophenyl,2,4,6-trihalophenyl, 2,3,4,6-tetrahalophenyl, 2,3,5,6-tetrahalophenyl,or 2,3,4,5,6-pentahalophenyl.

Still another preferred embodiment of this invention is the compounds,enantiomorphs, salts and complexes of in Formula I X is CH or N; Z is Oor NH; A is hydrogen; R₁ and R₂ are independently (C₁-C₄)alkyl; R₃, R₄and R₅ are hydrogen; R₇ is phenyl, phenylalkyl, or heterocyclic whereinat least one of the positions on the phenyl or heterocyclic ringadjacent to the bond to the cyclopropyl ring is a hydrogen substituent;and R₆ is (C₁-C₁₂)alkyl, halo(C₁-C₁₂)alkyl, (C₃-C₇)cycloalkyl,halo(C₃-C₇)cycloalkyl, (C₂-C,)alkenyl, halo(C₂-C₈)alkenyl,(C₂-C₈)alkynyl, or halo(C₂-C₈)alkynyl.

Another more preferred embodiment of this invention is the compounds,enantiomorphs, salts and complexes of Formula I wherein X is N; Z is NH;A is hydrogen; R₁ and R₂ is (CH₃); R₃, R₄ and R₅ are hydrogen; R₇ isphenyl, 2-substitutedphenyl, 3-substitutedphenyl, 4-substitutedphenyl,2,3-disubstitutedphenyl 2,4-disubstitutedphenyl,2,5-disubstitutedphenyl, 3,4-disubstitutedphenyl, 3,5-disubstituted,2,3,4-trisubstitutedphenyl, 2,3,5-trisubstitutedphenyl,2,4,5-trisubstitutedphenyl, 3,4,5-trisubstitutedphenyl, or2,3,4,5-tetrasubstitutedphenyl; and R₆is (C₁-C₄)alkyl orhalo(C₁-C₄)alkyl.

A second even more preferred embodiment of this invention is thecompounds, enantiomorphs, salts and complexes of Formula II wherein R₇is phenyl, 2-halophenyl, 3-halophenyl, 4-halophenyl, 2,3-dihalophenyl2,4-dihalophenyl, 2,5-dihalophenyl, 3,4-dihalophenyl, 3,5-dihalophenyl,2,3,4-trihalophenyl, 2,3,5-trihalophenyl, 2,4,5-trihalophenyl,3,4,5-trihalophenyl, or 2,3,4,5-tetrahalophenyl, and R₆is (C₁-C₄)alkyl.

A most preferred embodiment of this invention is the compounds,enantiomorphs, salts and complexes of Formula II wherein R₇ is phenyl,2-chlorophenyl, 3-chlorophenyl, or 4-chlorophenyl, and R₆ is CH₃.

Typical compounds of Formula I encompassed by the present inventionwherein A, R₃, R₄, and R₅ are hydrogen; X is CH and Z is O; and R₁ ismethyl include those compounds presented in Table 1 of Formula III whereR₂, R₆, and R₇ are defined in Table 1.

TABLE 1 Compd # R₂ R₆ R₇ 1.1 H CH₃ Ph 1.2 H CH₃ 4-Cl(Ph) 1.3 H CH₃4-Br(Ph) 1.4 H CH₃ 4-F(Ph) 1.5 H CH₃ 4-OCH₃(Pb) 1.6 H CH₃ 4-CF₃(Ph) 1.7H CH₃ 4-NO₂(Ph) 1.8 H CH₃ 2,4-Cl(Ph) 1.9 H CH₃ 2,4-F(Ph) 1.10 H CH₃3,4-F(Ph) 1.11 CH₃ CH₃ Ph 1.12 CH₃ CH₃ 2-Cl(Ph) 1.13 CH₃ CH₃ 3-Cl(Ph)1.14 CH₃ CH₃ 4-Cl(Pb) 1.15 CH₃ CH₃ 2-Br(Ph) 1.16 CH₃ CH₃ 3-Br(Ph) 1.17CH₃ CH₃ 4-Br(Ph) 1.18 CH₃ CH₃ 2-F(Ph) 1.19 CH₃ CH₃ 3-F(Ph) 1.20 CH₃ CH₃4-F(Ph) 1.21 CH₃ CH₃ 2-OCH₃(Ph) 1.22 CH₃ CH₃ 3-OCH₃(Ph) 1.23 CH₃ CH₃4-OCH₃(Ph) 1.24 CH₃ CH₃ 2-CH₃(Ph) 1.25 CH₃ CH₃ 3-CH₃(Ph) 1.26 CH₃ CH₃4-CH₃(Ph) 1.27 CH₃ CH₃ 2-CF₃(Ph) 1.28 CH₃ CH₃ 3-CF₃(Ph) 1.29 CH₃ CH₃4-CF₃(Ph) 1.30 CH₃ CH₃ 2-NO₂(Ph) 1.31 CH₃ CH₃ 3-NO₂(Ph) 1.32 CH₃ CH₃4-NO₂(Ph) 1.33 CH₃ CH₃ 2,3-Cl(Ph) 1.34 CH₃ CH₃ 2,4-Cl(Ph) 1.35 CH₃ CH₃2,5-Cl(Ph) 1.36 CH₃ CH₃ 3,4-Cl(Ph) 1.37 CH₃ CH₃ 3,5-Cl(Ph) 1.38 CH₃ CH₃2,3,5-Cl(Ph) 1.39 CH₃ CH₃ 2,3-F(Ph) 1.40 CH₃ CH₃ 2,4-F(Ph) 1.41 CH₃ CH₃2,5-F(Ph) 1.42 CH₃ CH₃ 3,4-F(Ph) 1.43 CH₃ CH₃ 3,5-F(Ph) 1.44 CH₃ CH₃2,4,5-F(Ph) 1.45 CH₃ CH₃ 2,4,5-Cl(Ph) 1.46 CH₃ CH₃ 3,4,5-Cl(Ph) 1.47 CH₃CH₃ 2,3,4,5-Cl(Ph) 1.48 CH₃ CH₃ 2,3,5-F(Ph) 1.49 CH₃ CH₃ 3,4,5-F(Ph)1.50 CH₃ CH₃ 2,3,4,5-F(Ph) 1.51 C₂H₅ CH₃ Ph 1.52 C₂H₅ CH₃ 2-Cl(Ph) 1.53C₂H₅ CH₃ 3-Cl(Ph) 1.54 C₂H₅ CH₃ 4-Cl(Ph) 1.55 C₂H₅ CH₃ 4-Br(Ph) 1.56C₂H₅ CH₃ 4-F(Ph) 1.57 C₂H₅ CH₃ 4-OCH₃(Ph) 1.58 C₂H₅ CH₃ 4-CH₃(Ph) 1.59C₂H₅ CH₃ 4-NO₂(Ph) 1.60 C₂H₅ CH₃ 2,4-Cl(Ph) 1.61 C₂H₅ CH₃ 2,4-F(Ph) 1.62n-C₃H₇ CH₃ Ph 1.63 n-C₃H₇ CH₃ 2-Cl(Ph) 1.64 n-C₃H₇ CH₃ 3-Cl(Ph) 1.65n-C₃H₇ CH₃ 4-Cl(Ph) 1.66 n-C₃H₇ CH₃ 4-F(Ph) 1.67 n-C₃H₇ CH₃ 3-OCH₃(Ph)1.68 n-C₃H₇ CH₃ 4-OCH₃(Ph) 1.69 n-C₃H₇ CH₃ 4-CH₃(Ph) 1.70 n-C₃H₇ CH₃4-NO₂(Ph) 1.71 n-C₃H₇ CH₃ 2,4-Cl(Ph) 1.72 n-C₃H₇ CH₃ 2,4-F(Ph) 1.73iso-C₃H₇ CH₃ Ph 1.74 iso-C₃H₇ CH₃ 2-Cl(Ph) 1.75 iso-C₃H₇ CH₃ 3-Cl(Ph)1.76 iso-C₃H₇ CH₃ 4-Cl(Ph) 1.77 iso-C₃H₇ CH₃ 4-Br(Ph) 1.78 iso-C₃H₇ CH₃4-F(Ph) 1.79 iso-C₃H₇ CH₃ 4-OCH₃(Ph) 1.80 iso-C₃H₇ CH₃ 4-CH₃(Ph) 1.81iso-C₃H₇ CH₃ 4-NO₂(Ph) 1.82 iso-C₃H₇ CH₃ 2,4-Cl(Ph) 1.83 iso-C₃H₇ CH₃2,4-F(Ph) 1.84 n-C₄H₉ CH₃ Ph 1.85 n-C₄H₉ CH₃ 2-Cl(Ph) 1.86 n-C₄H₉ CH₃3-Cl(Ph) 1.87 n-C₄H₉ CH₃ 4-Cl(Ph) 1.88 n-C₄H₉ CH₃ 4-Br(Ph) 1.89 n-C₄H₉CH₃ 4-F(Ph) 1.90 n-C₄H₉ CH₃ 4-OCH₃(Ph) 1.91 n-C₄H₉ CH₃ 4-CH₃(Ph) 1.92n-C₄H₉ CH₃ 4-NO₂(Ph) 1.93 n-C₄H₉ CH₃ 2,4-Cl(Ph) 1.94 n-C₄H₉ CH₃2,4-F(Ph) 1.95 iso-C₄H₉ CH₃ Ph 1.96 iso-C₄H₉ CH₃ 2-Cl(Ph) 1.97 iso-C₄H₉CH₃ 3-Cl(Ph) 1.98 iso-C₄H₉ CH₃ 4-Cl(Ph) 1.99 iso-C₄H₉ CH₃ 4-F(Ph) 1.100iso-C₄H₉ CH₃ 2-OCH₃(Ph) 1.101 iso-C₄H₉ CH₃ 3-OCH₃(Ph) 1.102 iso-C₄H₉ CH₃4-OCH₃(Ph) 1.103 iso-C₄H₉ CH₃ 4-CH₃(Ph) 1.104 iso-C₄H₉ CH₃ 2,4-Cl(Ph)1.105 iso-C₄H₉ CH₃ 2,4-F(Ph) 1.106 cyclopropyl CH₃ Ph 1.107 cyclopropylCH₃ 2-Cl(Ph) 1.108 cyclopropyl CH₃ 3-Cl(Ph) 1.109 cyclopropyl CH₃4-Cl(Ph) 1.110 cyclopropyl CH₃ 4-F(Ph) 1.111 cyclopropyl CH₃ 3-OCH₃(Ph)1.112 cyclopropyl CH₃ 4-OCH₃(Ph) 1.113 cyclopropyl CH₃ 4-CH₃(Ph) 1.114cyclopropyl CH₃ 4-NO₂(Ph) 1.115 cyclopropyl CH₃ 2,4-Cl(Ph) 1.116cyclopropyl CH₃ 2,4-F(Ph) 1.117 1-CH₃-cyclopropyl CH₃ Ph 1.1181-CH₃-cyclopropyl CH₃ 2-Cl(Ph) 1.119 1-CH₃-cyclopropyl CH₃ 3-Cl(Ph)1.120 1 -CH₃-cyclopropyl CH₃ 4-Cl(Ph) 1.121 1 -CH₃-cyclopropyl CH₃2-Br(Ph) 1.122 CN CH₃ Ph 1.123 CN CH₃ 2-Cl(Ph) 1.124 CN CH₃ 3-Cl(Ph)1.125 CN CH₃ 4-Cl(Ph) 1.126 CN CH₃ 2-Br(Ph) 1.127 CN CH₃ 3-Br(Ph) 1.128CN CH₃ 4-Br(Ph) 1.129 CN CH₃ 2-F(Ph) 1.130 CN CH₃ 3-F(Ph) 1.131 CN CH₃4-F(Ph) 1.132 CN CH₃ 2-OCH₃(Ph) 1.133 CN CH₃ 3-OCH₃(Ph) 1.134 CN CH₃4-OCH₃(Ph) 1.135 CN CH₃ 2-CH₃(Ph) 1.136 CN CH₃ 3-CH₃(Ph) 1.137 CN CH₃4-CH₃(Ph) 1.138 CN CH₃ 2-CF₃(Ph) 1.139 CN CH₃ 3-CF₃(Ph) 1.140 CN CH₃4-CF₃(Ph) 1.141 CN CH₃ 2-NO₂(Ph) 1.142 CN CH₃ 3-NO₂(Ph) 1.143 CN CH₃4-NO₂(Ph) 1.144 CN CH₃ 2,3-Cl(Ph) 1.145 CN CH₃ 2,4-Cl(Ph) 1.146 CN CH₃2,5-Cl(Ph) 1.147 CN CH₃ 3,4-Cl(Ph) 1.148 CN CH₃ 3,5-Cl(Ph) 1.149 CN CH₃2,3,5-Cl(Ph) 1.150 CN CH₃ 2,4,5-Cl(Ph) 1.151 CN CH₃ 3,4,5-Cl(Ph) 1.152CN CH₃ 2,3-F(Ph) 1.153 CN CH₃ 2,4-F(Ph) 1.154 CN CH₃ 2,5-F(Ph) 1.155 CNCH₃ 3,4-F(Ph) 1.156 CN CH₃ 3,5-F(Ph) 1.157 CN CH₃ 2,3,5-F(Ph) 1.158 CNCH₃ 2,4,5-F(Ph) 1.159 CN CH₃ 3,4,5-F(Ph) 1.160 CF₃ CH₃ Ph 1.161 CF₃ CH₃2-Cl(Ph) 1.162 CF₃ CH₃ 3-Cl(Ph) 1.163 CF₃ CH₃ 4-Cl(Ph) 1.164 CF₃ CH₃4-F(Ph) 1.165 CF₃ CH₃ 4-CH₃(Ph) 1.166 CH₃ C₂H₅ Ph 1.167 CH₃ C₂H₅2-Cl(Ph) 1.168 CH₃ C₂H₅ 3-Cl(Ph) 1.169 CH₃ C₂H₅ 4-Cl(Ph) 1.170 CH₃ C₂H₅4-F(Ph) 1.171 CH₃ C₂H₅ 2-OCH₃(Ph) 1.172 CH₃ C₂H₅ 3-OCH₃(Ph) 1.173 CH₃C₂H₅ 4-OCH₃(Ph) 1.174 CH₃ C₂H₃ 4-CH₃(Ph) 1.175 CH₃ C₂H₅ 4-NO₂(Ph) 1.176CH₃ C₂H₅ 2,4-Cl(Ph) 1.177 CH₃ C₂H₅ 2,4-F(Ph) 1.178 CH₃ n-C₃H₇ Ph 1.179CH₃ n-C₃H₇ 2-Cl(Ph) 1.180 CH₃ n-C₃H₇ 3-Cl(Ph) 1.181 CH₃ n-C₃H₇ 4-Cl(Ph)1.182 CH₃ n-C₃H₇ 4-F(Ph) 1.183 CH₃ n-C₃H₇ 3-OCH₃(Ph) 1.184 CH₃ n-C₃H₇4-OCH₃(Ph) 1.185 CH₃ n-C₃H₇ 4-CH₃(Ph) 1.186 CH₃ n-C₃H₇ 4-NO₂(Ph) 1.187CH₃ n-C₃H₇ 2,4-Cl(Ph) 1.188 CH₃ n-C₃H₇ 2,4-F(Ph) 1.189 CH₃ iso-C₃H₇ Ph1.190 CH₃ iso-C₃H₇ 4-Cl(Ph) 1.191 CH₃ n-C₄H₉ Ph 1.192 CH₃ n-C₄H₉4-Cl(Ph) 1.193 CH₃ iso-C₄H₉ Ph 1.194 CH₃ iso-C₄H₉ 4-Cl(Ph) 1.195 CN C₂H₅Ph 1.196 CN n-C₃H₇ Ph 1.197 CN iso-C₃H₇ Ph 1.198 CN n-C₄H₉ Ph 1.199 CNiso-C₄H₉ Ph 1.200 CF₃ C₂H₅ Ph 1.201 CF₃ n-C₃H₇ Ph 1.202 CF₃ iso-C₃H₇ Ph1.203 CF₃ n-C₄H₉ Ph 1.204 CF₃ iso-C₄H₉ Ph 1.205 H CF₃ Ph 1.206 CH₃ CF₃Ph 1.207 CN CF₃ Ph 1.208 CF₃ CF₃ Ph 1.209 H CH₂═CH Ph 1.210 CH₃ CH₂═CHPh 1.211 CN CH₂═CH Ph 1.212 CF₃ CH₂═CH Ph 1.213 H CH₃CH═CH Ph 1.214 CH₃CH₃CH═CH Ph 1.215 CN CH₃CH═CH Ph 1.216 CF₃ CH₃CH═CH Ph 1.217 H CH₃ PhCH₂1.218 H CH₃ 4-Cl(Ph)CH₂ 1.219 H CH₃ 4-Br(Ph)CH₂ 1.220 H CH₃ 4-F(Ph)CH₂1.221 H CH₃ 4-OCH₃(Ph)CH₂ 1.222 H CH₃ 4-CF₃(Ph)CH₂ 1.223 H CH₃4-NO₂(Ph)CH₂ 1.224 H CH₃ 2,4-Cl(Ph)CH₂ 1.225 H CH₃ 2,4-F(Ph)CH₂ 1.226 HCH₃ 3,4-F(Ph)CH₂ 1.227 CH₃ CH₃ PhCH₂ 1.228 CH₃ CH₃ 2-Cl(Ph)CH₂ 1.229 CH₃CH₃ 3-Cl(Ph)CH₂ 1.230 CH₃ CH₃ 4-Cl(Ph)CH₂ 1.231 CH₃ CH₃ 2-Br(Ph)CH₂1.232 CH₃ CH₃ 3-Br(Ph)CH₂ 1.233 CH₃ CH₃ 4-Br(Ph)CH₂ 1.234 CH₃ CH₃2-F(Ph)CH₂ 1.235 CH₃ CH₃ 3-F(Ph)CH₂ 1.236 CH₃ CH₃ 4-F(Ph)CH₂ 1.237 CH₃CH₃ 2,3-Cl(Ph)CH₂ 1.238 CH₃ CH₃ 2,4-Cl(Ph)CH₂ 1.239 CH₃ CH₃2,5-Cl(Ph)CH₂ 1.240 CH₃ CH₃ 3,4-Cl(Ph)CH₂ 1.241 CH₃ CH₃ 3,5-Cl(Ph)CH₂1.242 CH₃ CH₃ 2,3,5-Cl(Ph)CH₂ 1.243 CH₃ CH₃ 2,4,5-Cl(Ph)CH₂ 1.244 CH₃CH₃ 3,4,5-Cl(Ph)CH₂ 1.245 CH₃ CH₃ 2,3-F(Ph)CH₂ 1.246 CH₃ CH₃2,4-F(Ph)CH₂ 1.247 CH₃ CH₃ 2,5-F(Ph)CH₂ 1.248 CH₃ CH₃ 3,4-F(Ph)CH₂ 1.249CH₃ CH₃ 3,5-F(Ph)CH₂ 1.250 CH₃ CH₃ 2,3,5-F(Ph)CH₂ 1.251 CH₃ CH₃2,4,5-F(Ph)CH₂ 1.252 CH₃ CH₃ 3,4,5-F(Ph)CH₂ 1.253 CH₃ C₂H₅ PhCH₂ 1.254CH₃ n-C₃H₇ PhCH₂ 1.255 CH₃ iso-C₃H₇ PhCH₂ 1.256 CH₃ n-C₄H₉ PhCH₂ 1.257CH₃ iso-C₄H₉ PhCH₂ 1.258 CN C₂H₅ PhCH₂ 1.259 CN n-C₃H₇ PhCH₂ 1.260 CNiso-C₃H₇ PhCH₂ 1.261 CN n-C₄H₉ PhCH₂ 1.262 CN iso-C₄H₉ PhCH₂ 1.263 CF₃C₂H₃ PhCH₂ 1.264 CF₃ iso-C₃H₇ PhCH₂ 1.265 CF₃ n-C₃H₇ PhCH₂ 1.266 CF₃n-C₄H₉ PhCH₂ 1.267 CF₃ iso-C₄H₉ PhCH₂ 1.268 CH₃ CH₃ 4-Cl(Ph)CH₂ 1.269CH₃ C₂H₅ 4-Cl(Ph)CH₂ 1.270 CH₃ n-C₃H₇ 4-Cl(Ph)CH₂ 1.271 CH₃ iso-C₃H₇4-Cl(Ph)CH₂ 1.272 CH₃ n-C₄H₉ 4-Cl(Ph)CH₂ 1.273 CH₃ iso-C₄H₉ 4-Cl(Ph)CH₂1.274 CH₃ cyclopropyl 4-Cl(Ph)CH₂ 1.275 CN cyclopropyl 4-Cl(Ph)CH₂ 1.276CF₃ cyclopropyl 4-Cl(Ph)CH₂ 1.277 H CH₂═CH 4-Cl(Ph)CH₂ 1.278 CH₃ CH₂═CH4-Cl(Ph)CH₂ 1.279 CN CH₂═CH 4-Cl(Ph)CH₂ 1.280 CF₃ CH₂═CH 4-Cl(Ph)CH₂1.281 H CH₃CH═CH 4-Cl(Ph)CH₂ 1.282 CH₃ CH₃CH═CH 4-Cl(Ph)CH₂ 1.283 CNCH₃CH═CH 4-Cl(Ph)CH₂ 1.284 CF₃ CH₃CH═CH 4-Cl(Ph)CH₂ 1.285 CH₃ CH₃2,4-Cl(Ph)CH₂ 1.286 CH₃ C₂H₅ 2,4-Cl(Ph)CH₂ 1.287 CH₃ n-C₃H₇2,4-Cl(Ph)CH₂ 1.288 CH₃ iso-C₃H₇ 2,4-Cl(Ph)CH₂ 1.289 CH₃ n-C₄H₉2,4-Cl(Ph)CH₂ 1.290 CF₃ iso-C₄H₉ 2,4-Cl(Ph)CH₂ 1.291 CH₃ CH₂═CH2,4-Cl(Ph)CH₂ 1.288 CH₃ CH₃CH═CH 2,4-Cl(Ph)CH₂ 1.289 CN CH₃CH═CH2,4-Cl(Ph)CH₂ 1.290 CF₃ CH₃CH═CH 2,4-Cl(Ph)CH₂ 1.291 H CH₃ PhCH₂CH₂1.288 CH₃ CH₃ PhCH₂CH₂ 1.289 CH₃ C₂H₅ PhCH₂CH₂ 1.290 CH₃ n-C₃H₇ PhCH₂CH₂1.291 CH₃ iso-C₃H₇ PhCH₂CH₂ 1.292 CH₃ n-C₄H₉ PhCH₂CH₂ 1.293 CH₃ iso-C₄H₉PhCH₂CH₂ 1.294 CH₃ CH₂═CH PhCH₂CH₂ 1.295 CH₃ CH₃CH═CH PhCH₂CH₂ 1.296 CNCH₃ PhCH₂CH₂ 1.297 CN C₂H₅ PhCH₂CH₂ 1.298 CN n-C₃H₇ PhCH₂CH₂ 1.299 CNiso-C₃H₇ PhCH₂CH₂ 1.300 CF₃ CH₃ PhCH₂CH₂ 1.301 CF₃ C₂H₅ PhCH₂CH₂ 1.302CF₃ n-C₃H₇ PhCH₂CH₂ 1.303 CF₃ iso-C₃H₇ PhCH₂CH₂ 1.304 CF₃ n-C₄H₉PhCH₂CH₂ 1.305 CF₃ iso-C₄H₉ PhCH₂CH₂ 1.306 CF₃ CH₂═CH PhCH₂CH₂ 1.307 CF₃CH₃CH═CH PhCH₂CH₂ 1.308 cyclopropyl CH₃ PhCH₂CH₂ 1.309 cyclopropyl C₂H₅PhCH₂CH₂ 1.310 cyclopropyl n-C₃H₇ PhCH₂CH₂ 1.311 cyclopropyl iso-C₃H₇PhCH₂CH₂ 1.312 cyclopropyl n-C₄H₉ PhCH₂CH₂ 1.313 cyclopropyl iso-C₄H₉PhCH₂CH₂ 1.314 cyclopropyl CH₂═CH PhCH₂CH₂ 1.315 cyclopropyl CH₃CH═CHPhCH₂CH₂ 1.316 H CH₃ PhCH₂CH₂CH₂ 1.317 CH₃ CH₃ PhCH₂CH₂CH₂ 1.318 CH₃C₂H₅ PhCH₂CH₂CH₂ 1.319 CH₃ n-C₃H₇ PhCH₂CH₂CH₂ 1.320 CH₃ iso-C₃H₇PhCH₂CH₂CH₂ 1.321 CH₃ n-C₄H₉ PhCH₂CH₂CH₂ 1.322 CH₃ iso-C₄H₉ PhCH₂CH₂CH₂1.323 CH₃ CH₂═CH PhCH₂CH₂CH₂ 1.324 CH₃ CH₃CH═CH PhCH₂CH₂CH₂ 1.325 CN CH₃PhCH₂CH₂CH₂ 1.326 CN C₂H₅ PhCH₂CH₂CH₂ 1.327 CN n-C₃H₇ PhCH₂CH₂CH₂ 1.328CN iso-C₃H₇ PhCH₂CH₂CH₂ 1.329 CN n-C₄H₉ PhCH₂CH₂CH₂ 1.330 CN iso-C₄H₉PhCH₂CH₂CH₂ 1.331 CN CH₂═CH PhCH₂CH₂CH₂ 1.332 CN CH₃CH═CH PhCH₂CH₂CH₂1.333 CF₃ CH₃ PhCH₂CH₂CH₂ 1.334 CF₃ C₂H₅ PhCH₂CH₂CH₂ 1.335 CF₃ n-C₃H₇PhCH₂CH₂CH₂ 1.336 CF₃ iso-C₃H₇ PhCH₂CH₂CH₂ 1.337 CF₃ n-C₄H₉ PhCH₂CH₂CH₂1.338 CF₃ iso-C₄H₉ PhCH₂CH₂CH₂ 1.339 CF₃ CH₂═CH PhCH₂CH₂CH₂ 1.340 CF₃CH₃CH═CH PhCH₂CH₂CH₂

Table 2: Compounds 2.1 to 2.340 are compounds of Formula I wherein A,R₃, R₄, and R₅ are hydrogen; X is N and Z is O; R₁ is methyl; and R₂,R₆, and R₇ are defined as in Table 1. Compounds 2.11 (oil) and 2.14A(oil).

Table 3: Compounds 3.1 to 3.340 are compounds of Formula I wherein A,R₃, R₄, and R₅ are hydrogen; X is N and Z is NH, R₁ is methyl; and R₂,R₆, and R₇ are defined as in Table 1. Compounds 3.11 (oil, 4:1 A:Bisomers) and 3.14A (oil, 7:3 cis:trans cyclopropane isomers).

Typical compounds of Formula I encompassed by the present inventionwherein A, R₃, R₄, and R₅ are hydrogen; X is CH and Z is O; and R₁ ismethyl include those compounds presented in Table 4 of Formula III whereR₂, R₆, and R₇ are defined in Table 4.

TABLE 4 Compd # R₂ R₆ R₇ 4.1 H CH₃ 2-pyridyl 4.2 H CH₃ 3-pyridyl 4.3 HCH₃ 4-pyridyl 4.4 H CH₃ 2-pyrazinyl 4.5 H CH₃ 4-pyrimidinyl 4.6 H CH₃5-pyrimidinyl 4.7 H CH₃ 3-pyridazinyl 4.8 H CH₃ 4-pyridazinyl 4.9 H CH₃2-furyl 4.10 H CH₃ 3-furyl 4.11 H CH₃ 2-thienyl 4.12 H CH₃ 3-thienyl4.13 CH₃ CH₃ 2-pyridyl 4.14 CH₃ CH₃ 3-pyridyl 4.15 CH₃ CH₃ 4-pyridyl4.16 CH₃ CH₃ 2-pyrazinyl 4.17 CH₃ CH₃ 4-pyrimidinyl 4.18 CH₃ CH₃5-pyrimidinyl 4.19 CH₃ CH₃ 3-pyridazinyl 4.20 CH₃ CH₃ 4-pyridazinyl 4.21CH₃ CH₃ 2-furyl 4.22 CH₃ CH₃ 3-furyl 4.23 CH₃ CH₃ 2-thienyl 4.24 CH₃ CH₃3-thienyl 4.25 CH₃ CH₃ 1-CH₃-3-(1H)- 4.26 CH₃ CH₃ 1-CH₃-4-(1H)- 4.27 CH₃CH₃ 5-(1H)-pyrazolyl 4.28 CH₃ CH₃ 4-(1H)-imidazolyl 4.29 CH₃ CH₃5-(1H)-imidazolyl 4.30 CH₃ CH₃ 5-(1H)-pyrazolyl 4.31 CH₃ CH₃3-isothiazolyl 4.32 CH₃ CH₃ 4-isothiazolyl 4.33 CH₃ CH₃ 5-isothiazolyl4.34 CH₃ CH₃ 4-thiazolyl 4 35 CH₃ CH₃ 5-thiazolyl 4.36 CH₃ CH₃3-isooxazolyl 4.37 CH₃ CH₃ 4-isooxazolyl 4.38 CH₃ CH₃ 5-isooxazolyl 4 39CH₃ CH₃ 4-oxazolyl 4.40 CH₃ CH₃ 5-oxazolyl 4.41 CH₃ CH₃ 1-methyl-2-(1H)-4.42 CH₃ CH₃ 1-methyl-3-(1H)- 4.43 CH₃ CH₃ 2-quinolinyl 4.44 CH₃ CH₃3-quinolinyl 4.45 CH₃ CH₃ 4-quinolinyl 4.46 CH₃ CH₃ 3-Cl-pyrid-2-yl 4.47CH₃ CH₃ 2-Cl-pyrid-3-yl 4.48 CH₃ CH₃ 2-Cl-pyrid-4-yl 4.49 CH₃ CH₃4-Cl-furan-2-yl 4.50 CH₃ CH₃ 2-Cl-furan-3-yl 4.51 C₂H₃ CH₃ 2-pyridyl4.52 C₂H₃ CH₃ 3-pyridyl 4.53 C₂H₃ CH₃ 4-pyridyl 4.54 C₂H₃ CH₃ 2-furyl4.55 C₂H₃ CH₃ 3-furyl 4.56 C₂H₃ CH₃ 2-thienyl 4.57 C₂H₃ CH₃ 3-thienyl4.58 n-C₃H₇ CH₃ 2-pyridyl 4.59 n-C₃H₇ CH₃ 3-pyridyl 4.60 n-C₃H₇ CH₃4-pyridyl 4.61 n-C₃H₇ CH₃ 2-furyl 4.62 n-C₃H₇ CH₃ 3-furyl 4.63 n-C₃H₇CH₃ 2-thienyl 4.64 n-C₃H₇ CH₃ 3-thienyl 4.65 iso-C₃H₇ CH₃ 2-pyridyl 4.66iso-C₃H₇ CH₃ 3-pyridyl 4.67 iso-C₃H₇ CH₃ 4-pyridyl 4.68 iso-C₃H₇ CH₃2-furyl 4.69 iso-C₃H₇ CH₃ 3-furyl 4.70 iso-C₃H₇ CH₃ 2-thienyl 4.71iso-C₃H₇ CH₃ 3-thienyl 4.72 n-C₄H₉ CH₃ 2-pyridyl 4.73 n-C₄H₉ CH₃3-pyridyl 4.74 n-C₄H₉ CH₃ 4-pyridyl 4.75 n-C₄H₉ CH₃ 2-furyl 4.76 n-C₄H₉CH₃ 3-furyl 4.77 n-C₄H₉ CH₃ 2-thienyl 4.78 n-C₄H₉ CH₃ 3-thienyl 4.79iso-C₄H₉ CH₃ 2-pyridyl 4.80 iso-C₄H₉ CH₃ 3-pyridyl 4.81 iso-C₄H₉ CH₃4-pyridyl 4.82 iso-C₄H₉ CH₃ 2-furyl 4.83 iso-C₄H₉ CH₃ 3-furyl 4.84iso-C₄H₉ CH₃ 2-thienyl 4.85 iso-C₄H₉ CH₃ 3-thienyl 4.86 c-C₃H₅ CH₃2-pyridyl 4.87 c-C₃H₅ CH₃ 3-pyridyl 4.88 c-C₃H₅ CH₃ 4-pyridyl 4.89c-C₃H₅ CH₃ 2-furyl 4.90 c-C₃H₅ CH₃ 3-furyl 4.91 c-C₃H₅ CH₃ 2-thienyl4.92 c-C₃H₅ CH₃ 3-thienyl 4.93 CN CH₃ 2-pyridyl 4.94 CN CH₃ 3-pyridyl4.95 CN CH₃ 4-pyridyl 4.96 CN CH₃ 2-furyl 4.97 CN CH₃ 3-furyl 4.98 CNCH₃ 2-thienyl 4.99 CN CH₃ 3-thienyl 4.100 CF₃ CH₃ 2-pyridyl 4.101 CF₃CH₃ 3-pyridyl 4.102 CF₃ CH₃ 4-pyridyl 4.105 CF₃ CH₃ 2-thienyl 4.106 CF₃CH₃ 3-thienyl 4.107 CH₃ C₂H₅ 2-pyridyl 4.108 CH₃ C₂H₅ 3-pyridyl 4.109CH₃ C₂H₅ 4-pyridyl 4.110 CH₃ C₂H₅ 2-furyl 4.111 CH₃ C₂H₅ 3-furyl 4.112CH₃ C₂H₅ 2-thienyl 4.113 CH₃ C₂H₅ 3-thienyl 4.114 CH₃ n-C₃H₇ 2-pyridyl4.115 CH₃ n-C₃H₇ 3-pyridyl 4.116 CH₃ n-C₃H₇ 4-pyridyl 4.117 CH₃ n-C₃H₇2-furyl 4.118 CH₃ n-C₃H₇ 3-furyl 4.119 CH₃ n-C₄H₉ 2-pyridyl 4.120 CH₃n-C₄H₉ 3-pyridyl 4.121 CH₃ n-C₄H₉ 4-pyridyl 4.122 CH₃ n-C₄H₉ 2-thienyl4.123 CH₃ n-C₄H₉ 3-thienyl 4.124 CH₃ iso-C₄H₉ 2-pyridyl 4.125 CH₃iso-C₄H₉ 3-pyridyl 4.126 CH₃ iso-C₄H₉ 4-pyridyl 4.127 CH₃ iso-C₄H₉2-thienyl 4.128 CH₃ iso-C₄H₉ 3-thienyl 4.129 CH₃ cyclopropyl 2-pyridyl4.130 CH₃ cyclopropyl 3-pyridyl 4.131 CH₃ cyclopropyl 4-pyridyl 4 132CH₃ cyclopropyl 2-thienyl 4.133 CH₃ cyclopropyl 3-thienyl 4.134 CF₃ CH₃2-pyridyl 4.135 CF₃ CH₃ 3-pyridyl 4.136 CF₃ CH₃ 4-pyridyl 4.134 CF₃ CH₃2-furyl 4.135 CF₃ CH₃ 3-furyl 4.136 CF₃ CH₃ 2-thienyl 4.137 CF₃ CH₃3-thienyl 4.138 CF₃ C₂H₅ 2-pyridyl 4.139 CF₃ C₂H₅ 3-pyridyl 4.140 CF₃C₂H₅ 4-pyridyl 4.141 CF₃ C₂H₅ 2-furyl 4.142 CF₃ C₂H₅ 3-furyl 4.143 CF₃C₂H₅ 2-thienyl 4.144 CF₃ C₂H₅ 3-thienyl 4.145 CN CH₃ 2-pyridyl 4.146 CNCH₃ 3-pyridyl 4.147 CN CH₃ 4-pyridyl 4.148 CN CH₃ 2-furyl 4.149 CN CH₃3-furyl 4.150 CN CH₃ 2-thienyl 4.151 CN CH₃ 3-thienyl 4.152 CN C₂H₅2-pyridyl 4.153 CN C₂H₅ 3-pyridyl 4.154 CN C₂H₅ 4-pyridyl 4.155 CN C₂H₅2-furyl 4.156 CN C₂H₅ 3-furyl 4.157 CN C₂H₅ 2-thienyl 4.158 CN C₂H₅3-thienyl

Table 5: Compounds 5.1 to 5.158 are compounds of Formula I wherein A,R₃, R₄, and R₅ are hydrogen; X is N and Z is O; R₁ is methyl; and R₂,R₆, and R₇ are defined as in Table 4.

Table 6: Compounds 6.1 to 6.158 are compounds of Formula I wherein A,R₃, R₄, and R₅ are hydrogen; X is N and Z is NH, R₁ is methyl; and R₂,R₆, and R₇ are defined as in Table 4.

Typical compounds of Formula I encompassed by the present inventionwherein A, R₃, R₄, and R₅ are hydrogen; X is CH and Z is O; and R₁ ismethyl include those compounds presented in Table 7 of Formula III whereR₂, R₆, and R₇ are defined in Table 7

TABLE 7 Compd # R₂ R₆ R₇ 7.1 H H 2,6-Cl(Ph) 7.2 H H 2,3,6-Cl(Ph) 7.3 H H2,4,6-Cl(Ph) 7.4 H H 2,6-Br(Ph) 7.5 H H 2,3,6-Br(Ph) 7.6 H H2,4,6-Br(Ph) 7.7 H H 2,6-F(Ph) 7.8 H H 2,3,6-F(Ph) 7.9 H H 2,4,6-F(Ph)7.10 H H 2,6-CH₃(Ph) 7.11 H H 2,3,6-CH₃(Ph) 7.12 H H 2,4,6-CH₃(Ph) 7.13H H 2,6-CH₃O(Ph) 7.14 H H 2,3,6-CH₃O(Ph) 7.15 H H 2,4,6-CH₃O(Ph) 7.16CH₃ H 2,6-Cl(Ph) 7.17 CH₃ H 2,3,6-Cl(Ph) 7.18 CH₃ H 2,4,6-Cl(Ph) 7.19CH₃ H 2,6-Br(Ph) 7.20 CH₃ H 2,3,6-Br(Ph) 7.21 CH₃ H 2,4,6-Br(Ph) 7.22CH₃ H 2,6-F(Ph) 7.23 CH₃ H 2,3,6-F(Ph) 7.24 CH₃ H 2,4,6-F(Ph) 7.25 CH₃ H2,6-CH₃(Ph) 7.26 CH₃ H 2,3,6-CH₃(Ph) 7.27 CH₃ H 2,4,6-CH₃(Ph) 7.28 CH₃ H2,6-CH₃O(Ph) 7.29 CH₃ H 2,3,6-CH₃O(Ph) 7.30 CH₃ H 2,4,6-CH₃O(Ph) 7.31CH₃ H 2,6-NO₂(Ph) 7.32 CH₃ H 2,6-CN(Ph) 7.33 CH₃ H 2,3,6-CN(Ph) 7.34 CH₃H 2,4,6-CN(Ph) 7.35 CH₃ H 2,6-Ph(Ph) 7.36 CH₃ H 2,3,6-Ph(Ph) 7.37 CH₃ H2,4,6-Ph(Ph) 7.38 CH₃ H 2,6-PhO(Ph) 7.39 CH₃ H 2,3,6-PhO(Ph) 7.40 CH₃ H2,4,6-PhO(Ph) 7.41 CH₃ H 2,6-CF₃(Ph) 7.42 CH₃ H 2,3,6-CF₃(Ph) 7.43 CH₃ H2,4,6-CF_(3(Ph)) 7.44 CH₃ H 2,6-CF₃O(Ph) 7.45 CH₃ H 2,3,6-CF₃O(Ph) 7.46CH₃ H 2,4,6-CF₃O(Ph) 7.47 CH₃ H 2,3,4,6-Cl(Ph) 7.48 CH₃ H 2,3,5,6-Cl(Ph)7.49 CH₃ H 2,3,4,5,6-Cl(Ph) 7.50 CH₃ H 2,3,4,6-Ph(Ph) 7.51 CH₃ H2,3,5,6-Ph(Ph) 7.52 CH₃ H 2,3,4,5,6-Ph(Ph) 7.53 CH₃ H 2,3,4,6-PhO(Ph)7.54 CH₃ H 2,3,5,6-PhO(Ph) 7.55 CH₃ H 2,3,4,5,6-PhO(Ph) 7.56 CH₃ H2,3,4,6-Br(Ph) 7.57 CH₃ H 2,3,5,6-Br(Ph) 7.58 CH₃ H 2,3,4,5,6-Br(Ph)7.59 CH₃ H 2,3,4,6-F(Ph) 7.60 CH₃ H 2,3,5,6-F(Ph) 7.61 CH₃ H2,3,4,5,6-F(Ph) 7.62 CH₃ H 2,3,4,6-CH₃(Ph) 7.63 CH₃ H 2,3,5,6-CH₃(Ph)7.64 CH₃ H 2,3,4,5,6-CH₃(Ph) 7.65 CH₃ H 2,3,4,6-C₂H₅(Ph) 7.66 CH₃ H2,3,5,6-C₂H₅(Ph) 7.67 CH₃ H 2,3,4,5,6-C₂H₅(Ph) 7.68 CH₃ H2,3,4,6-CH₃O(Ph) 7.69 CH₃ H 2,3,5,6-CH₃O(Ph) 7.70 CH₃ H2,3,4,5,6-CH₃O(Ph) 7.71 CH₃ H 2,3,4,6-CF₃(Ph) 7.72 CH₃ H 2,3,5,6-CF₃(Ph)7.73 CH₃ H 2,3,4,5,6-CF₃(Ph) 7.74 CH₃ H 2,3,4,6-CF₃O(Ph) 7.75 CH₃ H2,3,5,6-CF₃O(Ph) 7.76 CH₃ H 2,3,4,5,6-CF₃O(Ph) 7.77 CH₃ H 2,3,4,6-CN(Ph)7.78 CH₃ H 2,3,5,6-CN(Ph) 7.79 CH₃ H 2,3,4,5,6-CN(Ph) 7.80 CH₃ H2-Br-6-Cl(Ph) 7.81 CH₃ H 2-Br-6-F(Ph) 7.82 CH₃ H 2-Br-6-CH₃(Ph) 7.83 CH₃H 2-Br-6-CF₃(Ph) 7.84 CH₃ H 2-Br-6-CH₃O(Ph) 7.85 CH₃ H 2-Br-6-CF₃O(Ph)7.86 CH₃ H 2-Br-6-CN(Ph) 7.87 CH₃ H 2-Cl-6-F(Ph) 7.88 CH₃ H2-Cl-6-CH₃(Ph) 7.89 CH₃ H 2-Cl-6-CF₃(Ph) 7.90 CH₃ H 2-Cl-6-CH₃O(Ph) 7.91CH₃ H 2-Cl-6-CF₃O(Ph) 7.92 CH₃ H 2-Cl-6-CN(Ph) 7.93 CH₃ H 2-F-6-CH₃(Ph)7.94 CH₃ H 2-F-6-CF₃(Ph) 7.95 CH₃ H 2-F-6-CH₃O(Ph) 7.96 CH₃ H2-F-6-CF₃O(Ph) 7.97 CH₃ H 6-CN,2F(Ph) 7.98 CH₃ H 2-CH₃-6-CF₃(Ph) 7.99CH₃ H 6-CH₃O-2-CH₃(Ph) 7.100 CH₃ H 2-CH₃-6-CF₃O(Ph) 7.101 CH₃ H6-CN-2-OCH₃(Ph) 7.102 CH₃ H 6-CN-2-CH₃(Ph) 7.103 CH₃ H 3,6-Cl-2-F(Ph)7.104 CH₃ H 3Cl-2,6-F(Ph) 7.105 CH₃ H 4-Cl-2,6-F(Ph) 7.106 CH₃ H2-Br-3,6-Cl(Ph) 7.107 CH₃ H 2,3-Br-6-Cl(Ph) 7.108 CH₃ H 3-Cl-2,6Br(Ph)7.109 CH₃ H 2,6-Cl-3-F(Ph) 7.110 CH₃ H 2,3-Cl-6-F(Ph) 7.111 CH₃ H2-Cl-3,6-F(Ph) 7.112 CH₃ H 3-Br-2,6-Cl(Ph) 7.113 CH₃ H 3-Br-2,6-F(Ph)7.114 CH₃ H 3-Br-6Cl-2-F(Ph) 7.115 CH₃ H 2-Br-5Cl-6-F(Ph) 7.116 CH₃ H2,6-Br-3-F(Ph) 7.117 CH₃ H 2,5-Br-6-F(Ph) 7.118 CH₃ H 2,4-Cl-6F(Ph)7.119 CH₃ H 2,6-Cl-4F(Ph) 7.120 CH₃ H 2,4-Cl-6Br(Ph) 7.121 CH₃ H2,6-Cl-4Br(Ph) 7.122 CH₃ H 2,4-F-6-Cl(Ph) 7.123 CH₃ H 2,4-F-6-Br(Ph)7.124 CH₃ H 2,6-F-4-Br(Ph) 7.125 CH₃ H 2,4-Br-6-F(Ph) 7.126 CH₃ H2,4-Br-6-Cl(Ph) 7.127 CH₃ H 2,6-Br-4-Cl(Ph) 7.128 CH₃ H 2,6-Br-4-F(Ph)7.129 CH₃ H 2,4-Cl-6-CH₃(Ph) 7.130 CH₃ H 2,6-Cl-4-CH₃(Ph) 7.131 CH₃ H2-Cl-4,6-(CH₃)₂(Ph) 7.132 CH₃ H 4-Cl-2,6-(CH₃)₂(Ph) 7.133 CH₃ H2,4-F-6-CH₃(Ph) 7.134 CH₃ H 2,6-F-4-CH₃(Ph) 7.135 CH₃ H2-F-4,6-(CH₃)₂(Ph) 7.136 CH₃ H 4-F-2,6-(CH₃)₂(Ph) 7.137 CH₃ H2,4-Br-6-CH₃(Ph) 7.138 CH₃ H 2,6-Br-4-CH₃(Ph) 7.139 CH₃ H2-Br-4,6-(CH₃)₂(Ph) 7.140 CH₃ H 4-Br-2,6-(CH₃)₂(Ph) 7.141 CH₃ H2,4-Cl-6-CF₃(Ph) 7.142 CH₃ H 2,6-Cl-4-CF₃(Ph) 7.143 CH₃ H2-Cl-4,6-(CF₃)₂(Ph) 7.144 CH₃ H 4-Cl-2,6-(CF₃)₂(Ph) 7.145 CH₃ H2,4-F-6-CF₃(Ph) 7.146 CH₃ H 2,6-F-4-CF₃(Ph) 7.147 CH₃ H2-F-3,6-(CF₃)₂(Ph) 7.148 CH₃ H 3-F-2,6-(CF₃)₂(Ph) 7.149 CH₃ H2,3-Br-6-CF₃(Ph) 7.150 CH₃ H 2,6-Br-3-CF₃(Ph) 7.137 CH₃ H2-Br-4,6-(CF₃)₂(Ph) 7.138 CH₃ H 4-Br-2,6-(CF₃)₂(Ph) 7.139 CH₃ H2,4-Cl-6-CF₃O(Ph) 7.140 CH₃ H 2,6-Cl-4-CF₃O(Ph) 7.141 CH₃ H2-Cl-4,6-(CF₃O)₂(Ph) 7.142 CH₃ H 4-Cl-2,6-(CF₃O)₂(Ph) 7.143 CH₃ H2,4-F-6-CF₃O(Ph) 7.144 CH₃ H 2,6-F-4-CF₃O(Ph) 7.145 CH₃ H2-F-4,6-(CF₃O)₂(Ph) 7.146 CH₃ H 4-F-2,6-(CF₃O)₂(Ph) 7.147 CH₃ H2,4-F-6-CF₃O(Ph) 7.148 CH₃ H 2,6-F-4-CF₃O(Ph) 7.149 CH₃ H2-F-4,6-(CF₃O)₂(Ph) 7.150 CH₃ H 4-F-2,6-(CF₃O)₂(Ph) 7.151 CH₃ H2-Br-3,4,6-Cl(Ph) 7.152 CH₃ H 6-F-2,4,5-Cl(Ph) 7.153 CH₃ H6-Cl-2,4,5-Br(Ph) 7.154 CH₃ H 6-F-2,4,5-Br(Ph) 7.155 CH₃ H2-Br-3,4,6-F(Ph) 7.156 CH₃ H 2-Cl-3,4,6-F(Ph) 7.157 CH₃ H6-CH₃-2,4,5-Cl(Ph) 7.158 CH₃ H 6-CH₃-2,4,5-Br(Ph) 7.159 CH₃ H6-CH₃-2,4,5-F(Ph) 7.160 CH₃ H 6-CF₃-2,4,5-Cl(Ph) 7.161 CH₃ H6-CF₃-2,4,5-Br(Ph) 7.162 CH₃ H 6-CF₃-2,4,5-F(Ph) 7.163 CH₃ H6-CF₃O-2,4,5-Cl(Ph) 7.164 CH₃ H 6-CF₃O-2,4,5-Br(Ph) 7.165 CH₃ H6-CF₃O-2,4,5-F(Ph) 7.166 CH₃ H 2-Br-3,5,6-Cl(Ph) 7.167 CH₃ H2-Br-3,5,6-F(Ph) 7.168 CH₃ H 2-Cl-3,5,6-F(Ph) 7.169 CH₃ H6-F-2,3,5-Cl(Ph) 7.170 CH₃ H 6-Cl-2,3,5-Br(Ph) 7.171 CH₃ H6-F-2,3,5-Br(Ph) 7.172 CH₃ H 6-CH₃-2,3,5-Cl(Ph) 7.173 CH₃ H6-CH₃-2,3,5-Br(Ph) 7.174 CH₃ H 2-CH₃-3,5,6-F(Ph) 7.175 CH₃ H6-CF₃-2,3,5-Cl(Ph) 7.176 CH₃ H 6-CF₃-2,3,5-Br(Ph) 7.177 CH₃ H2-CF₃-3,5,6-F(Ph) 7.178 CH₃ H 6-CF₃O-2,3,5-Cl(Ph) 7.179 CH₃ H6-CF₃O-2,3,5-Br(Ph) 7.180 CH₃ H 2-CF₃O-3,5,6-F(Ph) 7.172 CH₃ H4-Br-2,3,5,6-Cl(Ph) 7.173 CH₃ H 4-F-2,3,5,6-Cl(Ph) 7.174 CH₃ H4-Cl-2,3,5,6-Br(Ph) 7.175 CH₃ H 4-F-2,3,5,6-Br(Ph) 7.176 CH₃ H4-Cl-2,3,5,6-F(Ph) 7.177 CH₃ H 4-Br-2,3,5,6-F(Ph) 7.178 CH₃ H2-Br-3,4,5,6-Cl(Ph) 7.179 CH₃ H 2-F-3,4,5,6-Cl(Ph) 7.180 CH₃ H2-Cl-3,4,5,6-F(Ph) 7.181 CH₃ H 2-Br-3,4,5,6-F(Ph) 7.182 CH₃ H6-Cl-2,3,4,5-Br(Ph) 7.183 CH₃ H 6-F-2,3,4,5-Br(Ph) 7.184 CH₃ H4-CH₃-2,3,5,6-Cl(Ph) 7.185 CH₃ H 4-CH₃-2,3,5,6-Br(Ph) 7.186 CH₃ H4-CH₃-2,3,5,6-F(Ph) 7.187 CH₃ H 4-CF₃-2,3,5,6-Cl(Ph) 7.188 CH₃ H4-CF₃-2,3,5,6-Br(Ph) 7.189 CH₃ H 4-CF₃-2,3,5,6-F(Ph) 7.190 CH₃ H4-CF₃-2,3,5,6-Cl(Ph) 7.191 CH₃ H 4-CF₃O-2,3,5,6-Br(Ph) 7.192 CH₃ H4-CF₃O-2,3,5,6-F(Ph) 7.193 CH₃ H 4-CF₃O-2,3,5,6-Cl(Ph) 7.194 CH₃ H6-CH₃-2,3,4,5-Cl(Ph) 7.195 CH₃ H 6-CH₃-2,3,4,5-BrPh) 7.196 CH₃ H2-CH₃-3,4,5,6-F(Ph) 7.197 CH₃ H 6-CF₃O-2,3,4,5-Cl(Ph) 7.198 CH₃ H6-CF₃O-2,3,4,5-BrPh) 7.199 CH₃ H 2-CF₃O-3,4,5,6-F(Ph) 7.200 CH₃ CH₃2,6-Cl(Ph) 7.201 CH₃ CH₃ 2,3,6-Cl(Ph) 7.202 CH₃ CH₃ 2,4,6-Cl(Ph) 7.203CH₃ CH₃ 2,6-Br(Ph) 7.204 CH₃ CH₃ 2,3,6-Br(Ph) 7.205 CH₃ CH₃ 2,4,6-Br(Ph)7.206 CH₃ CH₃ 2,6-F(Ph) 7.207 CH₃ CH₃ 2,3,6-F(Ph) 7.208 CH₃ CH₃2,4,6-F(Ph) 7.209 CH₃ CH₃ 2,6-CH₃(Ph) 7.210 CH₃ CH₃ 2,3,6-CH₃(Ph) 7.211CH₃ C₂H₅ 2,4,6-CH₃(Ph) 7.212 CH₃ n-C₃H₇ 2,6-Cl(Ph) 7.213 CH₃ iso-C₃H₇2,3,6-Cl(Ph) 7.214 CH₃ n-C₄H₉ 2,4,6-Cl(Ph) 7.215 CH₃ iso-C₄H₉ 2,6-Cl(Ph)7.216 CH₃ CH₂═CH 2,3,6-Cl(Ph) 7.217 CH₃ CH₃CH═CH 2,4,6-Cl(Ph) 7.218 CN H2,6-Cl(Ph) 7.219 CN CH₃ 2,3,6-Cl(Ph) 7.220 CN C₂H₅ 2,4,6-Cl(Ph) 7.221 CNn-C₃H₇ 2,6-Cl(Ph) 7.222 CN iso-C₃H₇ 2,3,6-Cl(Ph) 7.223 CN n-C₄H₉2,4,6-Cl(Ph) 7.224 CN iso-C₄H₉ 2,6-Cl(Ph) 7.225 CN CH₂═CH 2,3,6-Cl(Ph)7.226 CN CH₃CH═CH 2,4,6-Cl(Ph) 7.227 CF₃ H 2,6-Cl(Ph) 7.228 CF₃ CH₃2,3,6-Cl(Ph) 7.229 CF₃ C₂H₅ 2,4,6-Cl(Ph) 7.230 CF₃ n-C₃H₇ 2,6-Cl(Ph)7.231 CF₃ iso-C₃H₇ 2,3,6-Cl(Ph)

Table 8: Compounds 8.1 to 8.231 are compounds of Formula I wherein A,R₃, R₄, and R₅ are hydrogen; X is N and Z is O; R₁ is methyl; and R₂,R₆, and R₇ are defined as in Table 7. Compounds 8.1 (oil, 9:1 A:Bisomers), 8.1A (oil), 8.1B (oil); 8.7 (oil, 7.9:2.1 A:B isomers).

Table 9: Compounds 9.1 to 9.231 are compounds of Formula I wherein A,R₃, R₄, and R₅ are hydrogen; X is N and Z is NH, R₁ is methyl; and R₂,R₆, and R₇ are defined as in Table 7. Compounds 9.1 (oil, 9:1 A:Bisomers), 9.1A (oil), 9.1B mpt 140-146° C.; 9.7A (oil) and 9.7B (oil).

Typical compounds of Formula I encompassed by the present inventionwherein A, R₃, R₄, and R₅ are hydrogen; X is CH and Z is O; and R₁ ismethyl include those compounds presented in Table 10 of Formula IIIwhere R₂, R₆, and R₇ are defined in Table 10.

TABLE 10 Compd # R₂ R₆ R₇ 10.1 H H 2,4-Cl-pyrid-3-yl 10.2 H H2,4-F-pyrid-3-yl 10.3 H H 2-Cl-4-F-pyrid-3-yl 10.4 H H2,4-(CH₃)₂-pyrid-3-yl 10.5 H H 3,5-Cl-pyrid-4-yl 10.6 H H3,5-F-pyrid-4-yl 10.7 H H 3-Cl-5-F-pyrid-4-yl 10.8 H H3,5-(CH₃)₂-pyrid-4-yl 10.9 H H 4,6-Cl-pyrimidin-5-yl 10.10 H H4,6-F-pyrimidin-5-yl 10.11 H H 4,6-(CH₃)₂-pyrimidin-5-yl 10.12 H H4-Cl-6-F-pyrimidin-5-yl 10.13 CH₃ H 2,4-Cl-pyrid-3-yl 10.14 CH₃ H2,4-F-pyrid-3-yl 10.15 CH₃ H 2-Cl-4-F-pyrid-3-yl 10.16 CH₃ H2,4-(CH₃)₂-pyrid-3-yl 10.17 CH₃ H 3,5-Cl-pyrid-4-yl 10.18 CH₃ H3,5-F-pyrid-4-yl 10.19 CH₃ H 3-Cl-5-F-pyrid-4-yl 10.20 CH₃ H3,5-(CH₃)₂-pyrid-4-yl 10.21 CH₃ H 4,6-Cl-pyrimidin-5-yl 10.22 CH₃ H4,6-F-pyrimidin-5-yl 10.23 CH₃ H 4,6-(CH₃)₂-pyrimidin-5-yl 10.24 CH₃ H4-Cl-6-F-pyrimidin-5-yl 10.25 CH₃ H 3,5-Cl-pyridazin-4-yl 10.26 CH₃ H3,5-F-pyridazin-4-yl 10.27 CH₃ H 3,5-Br-pyridazin-4-yl 10.28 CH₃ H3,5-(CH₃)₂-pyridazin-4-yl 10.29 CH₃ H 3-Cl-5-F-pyridazin-4-yl 10.30 CH₃H 5-Cl-3-F-pyridazin-4-yl 10.31 CH₃ H 3-Br-5-Cl-pyridazin-4-yl 10.32 CH₃H 5-Br-3-Cl-pyridazin-4-yl 10.33 CH₃ H 2,4-Cl-thien-3-yl 10.34 CH₃ H2,4-F-thien-3-yl 10.35 CH₃ CH₃ 2-Cl-4-F-thien-3-yl 10.36 CH₃ CH₃2-F-4-Cl-thien-3-yl 10.37 CH₃ CH₃ 2,4-(CH₃)₂-thien-3-yl 10.38 CH₃ CH₃2,4,5-Cl-thien-3-yl 10.39 CH₃ CH₃ 2,4,5-F-thien-3-yl 10.40 CH₃ CH₃2,4,5-CH₃-thien-3-yl 10.41 CH₃ CH₃ 2,4-Cl-furan-3-yl 10.42 CH₃ CH₃2,4-F-furan-3-yl 10.43 CH₃ CH₃ 2-Cl-4F-furan-3-yl 10.44 CH₃ CH₃2-F-4Cl-furan 3-yl 10.45 CH₃ CH₃ 2,4-(CH₃)₂-furan-3-yl 10.46 CH₃ CH₃2,4,5-Cl-furan-3-yl 10.47 CH₃ CH₃ 2,4,5-F-furan-3-yl 10.48 CH₃ CH₃2,4,5-CH₃-furan-3-yl 10.49 CH₃ CH₃ 2,4-Cl-1-CH₃-1H-pyrrol-3-yl 10.50 CH₃CH₃ 2,4-F-1-CH₃-1H-pyrrol-3-yl 10.51 CH₃ CH₃2-Cl-4F-1-CH₃-1H-pyrrol-3-yl 10.52 CH₃ CH₃ 2-F-4Cl-1-CH₃-1H-pyrrol-3-yl10.53 CH₃ CH₃ 3,5-Cl-isoxazol-4-yl 10.54 CH₃ CH₃ 3,5-F-isoxazol-4-yl10.55 CH₃ CH₃ 3,5-Br-isoxazol-4-yl 10.56 CH₃ CH₃ 3,5-CH₃-isoxazol-4-yl10.57 CH₃ CH₃ 3,5-CH₃O-isoxazol-4-yl 10.58 CH₃ CH₃3,5-CF₃O-isoxazol-4-yl 10.50 CH₃ CH₃ 3,5-Cl-isothiazol-4-yl 10.60 CH₃CH₃ 3,5-F-isothiazol-4-yl 10.61 CH₃ CH₃ 3,5-Br-isothiazol-4-yl 10.62 CH₃CH₃ 3,5-CH₃-isothiazol-4-yl 10.63 CH₃ CH₃ 3,5-CH₃O-isothiazol-4-yl 10.64CH₃ CH₃ 3,5-CF₃O-isothiazol-4-yl 10.66 CH₃ CH₃3,5-Cl-1-CH₃-1H-pyrazol-4-yl 10.67 CH₃ CH₃ 3,5-F-1-CH₃-1H-pyrazol-4-yl10.68 CH₃ CH₃ 3,5-Br-1-CH₃-1H-pyrazol-4-yl 10.69 CH₃ CH₃3-Cl-SF-1-CH₃-1H-pyrazl-4-yl 10.70 CH₃ CH₃ 2,4-Cl-pyrid-3-yl 10.71 CH₃C₂H₅ 2,4-F-pyrid-3-yl 10.72 CH₃ n-C₃H₇ 2-Cl-4-F-pyrid-3-yl 10.73 CH₃iso-C₃H₇ 2,4-(CH₃)₂-pyrid-3-yl 10.74 CH₃ n-C₄H₉ 3,5-Cl-pyrid-4-yl 10.75CH₃ iso-C₄H₉ 3,5-F-pyrid-4-yl 10.76 CH₃ CH₂═CH 3-Cl-5-F-pyrid-4-yl 10.77CN CH₃CH═CH 2,4-Cl-pyrid-3-yl 10.78 CN CH₃ 2,4-F-pyrid-3-yl 10.79 CN CH₃2-Cl-4-F-pyrid-3-yl 10.80 CN CH₃ 2,4-(CH₃)₂-pyrid-3-yl 10.81 CN CH₃3,5-Cl-pyrid-4-yl 10.82 CN CH₃ 3,5-F-pyrid-4-yl 10.83 CN CH₃3-Cl-5-F-pyrid-4-yl 10.84 CN CH₃ 4,6-Cl-pyrimidin-5-yl 10.85 CN CH₃4,6-F-pyrimidin-5-yl 10.86 CN CH₃ 2,4-Cl-thien-3-yl 10.87 CN CH₃2,4-F-thien-3-yl 10.88 CN CH₃ 2-Cl-4-F-thien-3-yl 10.89 CN CH₃2-F-4-Cl-thien-3-yl 10.90 CN CH₃ 2,4-(CH₃)₂-thien-3-yl 10.89 CN CH₃2,4,5-Cl-thien-3-yl 10.90 CN CH₃ 2,4,5-F-thien-3-yl 10.91 CN CH₃2,4,5-CH₃-thien-3-yl 10.92 CN C₂H₅ 2,4-Cl-pyrid-3-yl 10.93 CN n-C₃H₇2,4-Cl-pyrid-3-yl 10.94 CN iso-C₃H₇ 2,4-Cl-thien-3-yl 10.95 CN n-C₄H₉2,4-F-thien-3-yl 10.96 CN iso-C₄H₉ 2-Cl-4-F-thien-3-yl 10.97 CN CH₂═CH2-F-4-Cl-thien-3-yl 10.98 CN CH₃CH═CH 2,4-(CH₃)₂-thien-3-yl 10.99 CF₃CH₃ 2,4-Cl-pyrid-3-yl 10.100 CF₃ CH₃ 2,4-F-pyrid-3-yl 10.101 CF₃ CH₃2,4-Cl-thien-3-yl 10.102 CF₃ CH₃ 2,4-F-thien-3-yl 10.103 CF₃ CH₃2-Cl-4-F-thien-3-yl 10.104 CF₃ CH₃ 2-F-4-Cl-thien-3-yl 10.105 CH₃ CH₃2,4-(CH₃)₂-thien-3-yl 10.106 CH₃ CH₃ 3,5-Cl-isothiazol-4-yl 10.107 CH₃CH₃ 3,5-F-isothiazol-4-yl 10.108 CH₃ n-C₃H₇ 2,4-Cl-pyrid-3-yl 10.109 CH₃iso-C₃H₇ 2,4-F-pyrid-3-yl 10.110 CH₃ n-C₄H₉ 3,5-Cl-pyrid-4-yl 10.111 CH₃iso-C₄H₉ 3,5-F-pyrid-4-yl 10.112 CH₃ CH₂═CH 2,4-Cl-pyrid-3-yl 10.113 CH₃CH₃CH═CH 2,4-F-pyrid-3-yl

Table 11: Compounds 11.1 to 11.113 are compounds of Formula I wherein A,R₃, R₄, and R₅ are hydrogen; X is N and Z is O; R₁ is methyl; and R₂,R₆, and R₇ are defined as in Table 7.

Table 12: Compounds 12.1 to 12.113 are compounds of Formula I wherein A,R₃, R₄, and R₅ are hydrogen; X is N and Z is NH, R₁ is methyl; and R₂,R₆, and R₇ are defined as in Table 7.

As used in Tables 1 to 12 Ph is understood to be phenyl.

Compounds of the present invention are prepared according to thefollowing synthetic schemes. Scheme A describes the preparation ofcompounds of the Formula (I) where A and R₂ to R₇ are as defined inTables 1-2, 4-5, 7-8, and 10-11; X is CH or N, and Z is O (compounds ofFormula VI and VII). The cyclopropyl oximes (V) are reacted with theappropriately substituted benzyl derivatives (IV), where Z is a halogen,such as bromo, chloro or iodo, preferably a benzyl bromide. Acyclopropyl substituted oxime represented by the general formula (V) istreated, at room temperature, with an appropriate base to form an anion,followed by the addition of the benzyl bromide (IV). Typical basesemployed are metal hydrides such as sodium hydride, alkoxides such assodium methoxide and hydroxide bases such as sodium or potassiumhydroxide and alkali bases such as sodium or potassium carbonate.Typical solvents employed with hydride bases are N,N-dimethylformamide(DMF) and tetrahydrofuran (THF); with hydroxide bases DMF, THF, methylethyl ketone (MEK) and acetone and with alkali bases solvents such asDMF, acetone, and MEK.

As shown in Scheme A, the N—O bond in C(R₂)═N—O—, appears in the Eposition (assuming

is the larger substituent). It should be recognized that the Z isomercan also be produced as well as mixtures. When isomers are produced theyare designated isomer A (higher R_(f) on thin layer chromatography) andisomer B (lower R_(f) on thin layer chromatography). The determinationof which isomer, A or B possesses the E or Z geometry can be made bysuch conventional techniques as X ray crystallography or byspectroscopic means such as nuclear magnetic resonance spectroscopy. Forthe compounds of the present invention isomer A has been assigned the Eiminoxy configuration and isomer B, the Z iminoxy configuration.

Compounds of formula VI (X is CH) are prepared by alkylation with methylE-α-(2-bromomethylphenyl)-β-methoxyacrylate in the presence of a base,preferably NaOH or KOH, in a solvent, preferably acetone or methyl ethylketone. Methyl E-α-(2-bromomethylphenyl)-β-methoxyacrylate, as a singleE isomer, can be prepared in two steps from 2-methylphenylacetate asdescribed previously in U.S. Pat. No. 4,914,128, columns 3-4. Compoundsof formula VII (X=N) are prepared by the reaction with methylE-2-(bromomethyl)phenylglyoxylate O-methyloxime in the presence of abase, preferably NaOH or KOH, in a solvent, preferably acetone or methylethyl ketone. Methyl 2-(bromomethyl)phenylglyoxylate O-methyloxime canbe prepared as described in U.S. Pat. No. 4,999,042, columns 17-18 andU.S. Pat. No. 5,157,144, columns 17-18. Methyl2-(bromomethyl)phenylglyoxylate O-methyloxime is prepared from methyl2-methylphenyl-acetate by treatment with an alkyl nitrite under basicconditions to provide after methylation, methyl2-methyl-phenyl-glyoxalate O-methyl oxime which can also be preparedfrom methyl 2-methyl-phenylglyoxalate by treatment with 2-hydroxylaminehydrochloride and methylation or by treatment with methoxylaminehydrochloride.

As shown in scheme B compounds of formula IX (X is N) and of Tables 3,6, 9, and 12 can be prepared by the aminolysis of oximinoacetate (VII).The aminolysis of oximinoacetate to oximinoacetamides has been describedin U.S. Pat. No. 5,185,342, cols. 22, 48 and 57, U.S. Pat. No.5,221,691, cols. 26-27 and U.S. Pat. No. 5,407,902, col. 8. For example,compounds of formula VII and of Table 2 are treated with 40% aqueousmethylamine in methanol to provide compounds of formula IX and of Table3 of formula I where Z is NH. Alternatively, as is shown in scheme Bintermediate unsaturated oximes (V) are reacted with N-methyl(E)-2-methoxyimino-2-[2-(bromomethyl)phenyl]acetamide VIII in thepresence of a base such as an hydroxide base preferably in a solventsuch as acetone or methyl ethyl ketone to provide compounds of formula(IX). N-methyl (E)-2-methoxy-imino-2-[2-(bromomethyl)phenyl]acetamide isdescribed in U.S. Pat. No. 5,387,714, col. 13.

The oximes of the general formula (V) can be obtained, as shown inScheme C, by reacting the corresponding cyclopropyl aldehyde or ketone(X) with hydroxylamine hydrochloride from room temperature to reflux,preferably at room temperature, in an appropriate solvent such asmethanol or ethanol in the presence of an appropriate alkali such assodium hydroxide, potassium carbonate or pyridine. A general descriptionof the synthesis of oximes with hydroxylamine is described in March,Advanced Organic Chemistry, 4th Ed, pp. 906-907 and references therein.The oximes of the general formula (III) when obtained as a mixture ofsyn or anti oxime isomers can be separated into individual isomers andalkylated as described in scheme A and B. When a mixture of oximes ofthe general formula (III) are used in Schemes A and B the compounds ofthe formula VI, VII and IX can be separated into their individualisomers by conventional chromatographic techniques.

The cyclopropyl aldehydes or ketones (X) are prepared by conventionaltechniques. The unsaturated intermediate XI (Scheme D) is reacted with asulfur ylide, prepared from a dimethylsulfoxonium salt in the presenceof a base, resulting in the substituted acyl cyclopropanes, X, as shownin Scheme D. The chemistry of sulfur ylides is described in Trost andMelvin, Sulfur Ylids, Academic Press, New York, N.Y. 1975 and in Block,Reactions of Organosulfur Compounds, pp. 91-123, Academic Press, NewYork, N.Y. 1978. Typical reaction conditions for sulfur ylide formationfrom a dimethylsulfoxonium salt utilizes bases such as hydroxides, metalhydrides and alkoxides in solvents such as dimethoxyethane,dimethylsulfoxide and water depending on the base employed. Thereactions are conducted from 0 to 20° C. preferably from 10-15° C. andpreferably with alkali metal hydroxides in dimethylsulfoxide. Typicallydimethylsulfoxonium methylide is prepared from trimethylsulfoxoniumiodide in dimethylsulfoxide in the presence of powdered sodium hydroxideat room temperature. The unsaturated aldehydes or ketones (XI) are addeddropwise to the ylide and stirred at room temperature.

The α,β-unsaturated aldehydes or ketones XI can be prepared byconventional condensation techniques. A extensive description of thesynthesis of α,β-unsaturated aldehydes or ketones (enones) is describedin March, Advanced Organic Chemistry, 4th Ed, pp. 937-955 and referencestherein. For example Organic Reactions, Volume 16 describes the generalaldol condensation of ketones and aldehydes. For intermediates offormula XI of this invention, in general the ketones and aldehydes areR₇COR₆ (XII) and R₂COCH₂R₃ (XIII) where R₂, R₃, R₆, and R₇ are definedpreviously. When R₆ is hydrogen, the aldehydes R₇CHO (XIV), are forexample benzaldehydes (arylCHO) or heterocyclic aldehydes substitutedwith from 2 to 5 substituents wherein the positions on the aryl andheterocyclic ring adjacent to the bond to the cyclopropyl ring, inFormula I, are both substituted. These substituted benzaldehyes orheterocyclic aldehydes are commerically available or prepared byconventional techniques. The aldehydes R₇CHO (XIV) are reacted with theketones R₂COCH₂R₃, XIII, (as shown in Scheme E) to provide theintermediates enones XV. Typically the ketone, R₂COCH₂R₃, is dissolvedin a hydroxylic solvent, such as methanol or ethanol, to which is addeddropwise the aldehyde R₇CHO followed by the base or alternatively asolution of the aldehyde in an aqueous basic solution is added. Thetypical bases used can be alkali metal hydroxides, such as barium,potassium or sodium hydroxide and the dropwise addition is conductedfrom 0° C. to 35° C. preferably at ambient temperature. When the enoneis derived from acetone (R₂ is methyl and R₃ is hydrogen) the solventcan be acetone to which is added R₇COR₆ followed by the aqueoushydroxide solution. Preferably the aldehyde is dissolved in a solventmixture of acetone:water (1:5) to which is added the base while stirringat room temperature.

When R₆ is not hydrogen, R₇COR₆ (XII) are the ketones arylCOR₆ orheterocyclic ketones, substituted with from 2 to 5 substituents whereinthe positions on the aryl and heterocyclic rings adjacent to the bond tothe cyclopropyl ring, in Formula I, are both substituted or aryl orheterocyclic ring is unsubstituted or substituted from 1 to 4substituents wherein at least one of the positions on the aryl orheterocyclic rings adjacent to the bond to the cyclopropyl ring, inFormula I, is a hydrogen. For the compounds of formula I where R₆ is nothydrogen the intermediate unsaturated aldehydes and ketones XI areprepared, as shown in Scheme F, according to the procedures described inU.S. Pat. No. 3,950,427, col. 17 line 20, to provide after purificationthe E diastereiosmer (R₇ is trans to R₂CO in XI). In a typicalpreparation a ketone such as R₇COR₆ is reacted with an ethyl trans3-ethoxycrotonate in dimethylformamide in the presence of potassiumt-butoxide followed by acidic hydrolysis and decarboxylation to give XI.The crotonates, XVI, can be prepared from substituted ethyl acetoketonesby conventional techniques

Alternatively the α,β-unsaturated cyclopropyl ketones X can be preparedfrom cyclopropyl nitriles XIV which are prepared via cyclopropanation ofthe acrylonitriles XVIII as is described in Scheme G. The acrylonitrilesXVIII starting materials, shown in Scheme G can be prepared byconventional synthetic methods as described in March, Advanced OrganicChemistry, 4th Ed, pp. 937-955 and references therein. For example thenitrile derivative R₃CH₂CN is condensed with the ketone or aldehydeR₇COR₆, in the presence of a base to provide the acrylonitriles XIII.Typically the a nitrile is dissolved in a solvent such as ethanol andwater to which is added the aldehyde or ketone followed by a base.Typical bases used can be alkali metal hydroxides, such as barium,potassium or sodium hydroxide and the mixture is stirred typically atambient temperature.

The acrylonitrile XVIII is treated as is described in Scheme D with asulfur ylide to provide the cyclopropyl nitriles XVII. The cyclopropylnitrile XVII is transformed to the cyclopropyl ketone by organometallicaddition to the nitrile followed by hydrolysis. For example the standardGrignard reagents R₂MgX or organolithium reagents, R₂Li, add to thenitrile functionality to provide the ketone X. The addition reaction tonitriles is described in March, Advanced Organic Chemistry, 4th Ed,pp.935-936 and references cited therein. The cyclopropyl nitrile XVIIcan be transformed to the cyclopropyl aldehyde X′ (where R₂ is H) bystandard reductive methods such as with diisobutylaluminum hydride(DiBAL). The formation of aldehydes from the reduction of nitrites isdescribed in March, Advanced Organic Chemistry, 4th Ed, pp.919-920 andreferences cited therein.

A direct synthesis of compounds of the formula VII or IX is shown inScheme H. Compounds of the Formula VII or IX can be prepared directlyfrom the functionalized cyclopropyl ketones or aldehydes, X, bycondensation with the aminoxy intermediate XIX. The preparation ofaminoxy intermediate XIX is described in U.S. Pat. No. 5,194,662. Theaminoxy intermediate XIX is prepared in a two step sequence by thealkylation of IV (where X is N) with N-hydroxyphthalimide which istreated with hydrazine to provide XIX. The aminoxy intermediate XIX iscondensed with ketones or aldehydes X to provide VII which are treatedas shown in scheme B to provide IX.

The compounds of this invention can be made according to the followingprocedures:

EXAMPLE 1 Preparation of E and Z imine isomers: (E,E) and (Z,E) Methyl2-[2-((trans-1-(2-(2′,6′-dichlorophenyl)cyclopropyl)ethylidene)aminooxymethyl)phenal]-2-methoxyiminoacetateCompound 8.1, 8.1A and 8.1B of Table 8

Preparation of 4-(2,6-dichlorophenyl)-3-buten-2-one

To a 1000 ml round bottom flask equipped with mechanical stirrer, andnitrogen inlet were charged 26.5 g (0.15 moles) of 4-chlorobenzaledhyde,125 mls of acetone,600 mls of water, and 9.3 g (0.23 moles) of sodiumhydroxide. The mixture was stirred for 12 hours at room temperature.Analysis of an aliquot by GC indicated complete reaction. The resultingsolid was collected by vacuum filtration, and washed with 100 mls ofwater, 100 mls of hexane, and dried in vacuuo at 40° C. for 3 hours.31.4 g of the title compound, 4-(2,6-dichlorophenyl)-3-buten-2-one, wasisolated as a pale yellow solid in 98% isolated yield.

NMR 300 MHz ¹H CDCl₃ 2.43 (s, 3H); 6.80 (d, 1H); 7.18-7.38 (m, 1H); 7.4(d, 2H); 7.6 (d, 1H).

Preparation of trans-1-(2,6 dichlorophenyl)-2-acetyl-cyclopropane

To a 1000 ml round bottom flask equipped with magnetic stirrer, nitrogeninlet and addition funnel were charged 33.2 g (0.151 moles) of trimethylsulfoxonium iodide, 6.1 g (0.151 moles) of powdered sodium hydroxide,and 300 mls DMSO. The mixture was stirred at room temperature for 1hour, followed by the rapid addition of the4-(2,6-dichlorophenyl)-3-buten-2-one (32.3 g, 0.151 moles) in oneportion. The reaction was then stirred for 10 minutes at ambienttemperature, then poured into 200 mls of ice water and extracted with3×100 ml of ethyl ether. The ether extract was washed with 2×100 mls ofwater, 100 mls of brine, dried over anhydrous MgSO₄, filtered through 2″of silica gel, and concentrated in vacuuo on a rotary evaporator toafford 31.7 g of a thick pale yellow oil which was chromatographed onsilica gel with 90% hexane, 10% ethyl acetate. The pure fractions werecombined and concentrated in vacuuo on a rotary evaporator to afford27.9 g of trans-1-(2,6 dichlorophenyl)-2-acetyl-cyclopropane as a freeflowing pale yellow liquid in 81% yield.

NMR 300 MHz ¹H CDCl₃ 1.4-1.48 (m, 1H); 1.78-1.86 (m, 1H); 2.21-2.30 (m,1H); 2.34-2.4 (m, 1H); 2.41 (s, 3H), 7.2 (m, 1H), 7.3 (d, 2H).

Preparation of E and Z imine isomers: (E,E) and (Z,E) Methyl2-[2-((trans-1-(2-(2′,6′-dichlorophenyl)cyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetate

To a 100 ml round bottom flask equipped with magnetic stirrer werecharged 1.0 g (0.0044 moles) of the trans-1-(2,6dichlorophenyl)-2-acetyl-cyclopropane, 1.1 g (0.0044 moles) of themethyl (E)-2-(aminooxymethyl)phenyl glyoxylate O-methyloxime, and 50 mlsof anhydrous methanol. The reaction was stirred overnight at roomtemperature. Analysis of an aliquot by GC indicated no starting materialand two new products. The reaction was then poured into 100 mls of waterand extracted with 3×50 ml of ethyl ether. The ether extract was washedwith 100 mls of water, 100 mls of 0.1N HCl, and 100 mls of brine, driedover anhydrous magnesium sulfate, filtered, and concentrated in vacuuoon a rotary evaporator to afford 2.0 g of a thick yellow oil which waschromatographed on silica with 20% ethyl acetate/80% hexane. The purefractions were combined and concentrated in vacuuo on a rotaryevaporator to afford 1.4 g of the methyl2-[2-((trans-1-(2-(2′,6′-dichlorophenyl)cyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetateas a pale yellow oil as a 90/10 A:B (E,E:E,Z) isomer ratio in 72%isolated yield.

NMR 300 MHz ¹H CDCl₃ 1.3 (m, 1H); 1.7 (m, 1H); 1.85 (s, 3H); 1.95 (m,1H); 2.2 (m, 1H); 3.85 (s, 3H), 4.1 (s, 3H); 5.0 (s, 2H); 7.1 (m, 1H),7.2 (m, 1H); 7.3 (d, 2H); 7.4-7.6 (m, 3H).

An additional 10.0 g of the crude product as an orange oil (85%chemically pure and 2:1 A:B isomers) was chromatographed on silica with20% ethyl acetate/80% hexane.

5.02 grams of isomer A as a pale yellow oil was collected (E:E)-methyl2-[2-((trans-1-(2-(2′,6′-dichlorophenyl)cyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetate.

Compound 8.1A, Isomer A, E imine, NMR (300 MHz., ¹H CDCl₃): 1.19-1.30(1H, m), 1.50-1.58 (1H, m), 1.75-1.85 (1H, m) 1.84 (3H, s), 2.06-2.14(1H, m), 3.85 (3H, s), 4.05 (3H, s), 4.98 (2H, s), 7.03-7.49 (7H, m).

0.825 grams of isomer B as a pale yellow oil was collected (Z:E)-methyl2-[2-((trans-1-(2-(2′,6′-dichlorophenyl)cyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetate.

Compound 8.1B, Isomer B, Z imine, NMR (300 MHz., ¹H CDCl₃): 1.21-1.28(1H, m), 1.40-1.52 (1H, m), 1.70 (3H, s), 2.18-2.23 (1H, m) 2.61-2.70(1H, m), 3.80 (3H, s), 4.00 (3H, s), 4.97 (2H, s), 7.05-7.52 (7H, m).

Preparation of methyl (E)-2-(aminooxymethyl)phenyl glyoxylateO-methyloxime Methyl (E)-2-(O-phthalimidoxymethyl)phenyl glyoxylateO-methyloxime

To a dry 500 ml round bottom flask equipped with magnetic stirrer, andnitrogen inlet were charged 5.1 g (0.0315 moles) ofN-hydroxyphthalimide, 1.3 g (0.0315 moles) of sodium hydroxide, and 300ml of anhydrous dimethylformamide. The dark red solution was stirred atambient temperature for 20 min., followed by the addition of the methyl2-(bromomethyl)phenylglyoxylate O-methyloxime (15 g, 60% pure, 0.0315moles) in one portion. The reaction was stirred at ambient temperatureover the weekend, then poured into 800 mls of water and stirred for 1hour to afford a white solid which was collected by vacuum filtrationand washed with water, hexane, and dried under vacuum at 40° C.overnight. Isolated 11.5 g of a white solid (98% isolated yield) whichwas consistent with the desired product, methyl(E)-2-(O-phthalimidoxymethyl)phenyl glyoxylate O-methyloxime, uponanalysis by 300 MHz

¹H NMR (300 MHz, ¹H, CDCl₃, TMS=0 ppm) 3.8 (s, 3H), 3.95 (s, 3H), 5.0(s, 2H), 7.1 (d, 1H), 7.5 (m, 2H), 7.7-7.9 (m, 5H).

Preparation of methyl (E)-2-(aminooxymethyl)phenyl glyoxylateO-methyloxime

To a 250 ml round-bottom flask equipped with magnetic stirrer werecharged 11.4 g (0.031 moles)of methyl(E)-2-(O-phthalimidoxymethyl)phenyl glyoxylate O-methyloxime 100 mls ofanhydrous methanol, and 1.9 g (0.034 moles) of hydrazine monohydrate.The flask was stoppered, and the reaction was stirred at ambienttemperature for 2 hours. The resulting solid was removed by filtrationand the filtrate was concentrated on the rotary evaporator. The residuewas dissolved in 100 mls of ether, filtered, and stripped to afford 7.4g of a thick yellow oil (100% isolated yield). which was consistent withthe desired product methyl (E)-2-(aminooxymethyl)phenyl glyoxylateO-methyloxime upon analysis by 300 MHz ¹H NMR. Stored at −20° C. untilneeded for future synthesis.

NMR (300 MHz, 1H, CDCl₃, TMS=0 ppm) 3.87 (s, 3H), 4.03 (s, 3H), 4.6 (s,2H), 4.9-5.4 (bs, 2H), 7.2 (m, 1H), 7.4-7.5 (m, 3H).

EXAMPLE 2 Preparation of E and Z imine isomers: (E,E) and (Z,E)-N-Methyl2-[2-((trans-1-(2-(2′,6′-dichlorophenyl)cyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetamideCompounds 9.1, 9.1A, 9.1B of Table 9

To a 100 ml flask equipped with magnetic stirrer and were charged 0.7 g(0.00115 moles) of (E,E:Z,E)-methyl2-[2-((trans-1-(2-(2′,6′-dichlorophenyl)cyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetate,50 mls of methanol, and 2 mls (0.026 moles) of 40% aqueous methyl aminesolution. The mixture stirred at ambient temperature overnight, thenpoured into 200 mls of water and extracted with 3×100 ml of ethyl ether.The ether extract was washed with 2×100 mls of water, 100 mls of 0.1 NHCl, and 100 mls of brine, dried over anhydrous MgSO₄, filtered, andconcentrated in vacuuo on a rotary evaporator to afford 0.6 g ofN-Methyl2-[2-((trans-1-(2-(2′,6′-dichlorophenyl)cyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetamideas a thick viscous pale yellow oil. 90/10 A:B (E,E:Z,E) isomers ratio in88% isolated yield.

NMR 300 MHz, ¹H CDCl₃ 1.2 (m, 1H); 1.6 (m, 1H); 1.8 (s, 3H); 1.9 (m,1H); 2.2 (m, 1H); 2.9 (d, 3H); 3.95 (s, 3H), 5.0 (s, 2H); 6.7 (bs, 1H);7.1 (m, 1H), 7.2 (m, 1H); 7.3 (d, 2H); 7.4-7.6 (m, 3H).

Additionally each of 8.1A and 8.1B oxime esters was separately treatedas above with methylamine.

Aminolysis of 5.01 grams of 8.1A (E,E isomer) gave 5.02 grams (100%yield) of (E,E)-N-methyl2-[2-((trans-1-(2-(2′,6′-dichlorophenyl)cyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetamideas an oil. The oil was treated with ether, concentrated and cooled indry ice followed by the addition of hexane to complete thecrystallization. The resulting crystals were filtered to give a solidmpt. 94-97° C. Compound 9.1A, Isomer A, E,E isomer, NMR (300 MHz, ¹HCDCl₃): 1.20-1.30 (1H, m), 1.51-1.58 (1H, m), 1.80-1.89 (1H, m), 1.82(3H, s), 2.2 (1H,m), 2.89 (3H, d), 3.96 (3H, s), 4.98 (2H, s), 6.70 (1H,br), 7.05-7.48 (7H, m).

Aminolysis of 0.825 grams of 8.1B (Z,E isomer) gave 0.825 grams (100%yield) of (Z,E)-N-methyl2-[2-((trans-1-(2-(2′,6′-dichlorophenyl)cyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetamideas solid, mpt. 140-146° C. Compound 9.1B, Isomer B, Z,E isomer, NMR (300MHz, ¹H CDCl₃):): 1.22-1.30 (1H, m), 1.40-1.51 (1H, m), 1.70 (3H, s),2.15-2.23 (1H, m), 2.60-2.69 (1H,m), 2.85 (3H, d), 3.90 (3H, s), 4.97(2H, s), 6.70 (1H, br), 7.09-7.51 (7H, m).

EXAMPLE 3 Preparation of E and Z imine isomers: (E,E) and (Z,E) Methyl2-[2-((trans-1-(2-(2′,6′-difluorophenyl)cyclopropylethylidene)aminooxymethylphenyl]-2-methoxyiminoacetateCompound 8.7 of Table 8

Preparation of 4-(2,6-difluorophenyl)-3-buten-2-one

To a 100 ml reaction bottle equipped with magnetic stir bar were charged5.0 g (35.2 mmole) 2,6-difluorobenzaldehyde in 20 ml acetone, added 50%NaOH (42 mmole) in 60 ml water (exothermic) and stirred roomtemperature. The reaction was monitored by GLC and after 2 hours workedup. The reaction mixture was extracted with 50 ml CHCl₃, washed with 50ml H₂O, dried over anhydrous MgSO₄, filtered, and removed solvent invacuuo on a rotary evaporator to afford 5.7 g of4-(2,6-difluoro-phenyl)-3-buten-2-one as a yellow oil (81% purity by GC)in 89.5% isolated yield.

NMR (300 MHz ¹H CDCl₃): 2.4 (s, 3H); 6.9 (m, 3H); 7.3 (m, 1H); 7.6 (d,1H).

Preparation of trans-1-(2,6 difluorophenyl)-2-acetyl-cyclopropane

To a 500 ml round bottom flask equipped with magnetic stirrer, nitrogeninlet and addition funnel was charged 2.47 g (11.2 mmoles) of trimethylsulfoxonium iodide, 0.448 g (11.2 mmole) of powdered sodium hydroxide,and 50 mls DMSO. The mixture was stirred at room temperature for 0.5hour, followed by the rapid addition of 2.04 g (11.2 mmole)2,6-difluoro-phenyl-3-buten-2-one in 25 ml DMSO in one portion. Thereaction was stirred for 15 minutes at ambient temperature, poured into200 mls of ice water, and then extracted with 150 ml of ethyl ether. Theether extract was washed with 4×100 mls of water, dried over anhydrousMgSO₄, filtered, and concentrated in vacuuo on a rotary evaporator toafford 1.3 g crude product as a yellow oil. This was combined with 1.6 gfrom a similar reaction and the total crude of 2.9 g was chromatographedon silica with CH₂Cl₂. Fractions (#5-9) were combined and concentratedin vacuuo on a rotary evaporator to afford 1.5 g (92% purity by GC) oftrans-1-(2,6 difluorophenyl)-2-acetylcyclopropane as a free flowing paleyellow liquid, in 28.8% yield.

NMR (300 MHz ¹H CDCl3): 1.6 (m, 2H); 2.3 (s, 3H); 2.4 (m, 2H); 6.8 (m,2H), 7.1 (m, 1H).

Preparation of E and Z imine isomers: (E,E) and (Z,E) Methyl2-[2-((trans-1-(2-(2′,6′-difluorophenyl)cyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetate

To a 25 ml reaction vial equipped with magnetic stirrer were charged 1.0g (0.0051 moles) of the trans-1-(2,6difluorophenyl)-2-acetyl-cyclopropane and 1.33 g (0.0056 moles) of themethyl (E)-2-(aminooxymethyl)phenyl glyoxylate O-methyloxime in 5 mls ofanhydrous methanol and 5 drops glacial acetic acid. The reaction wasstirred 4 hours at room temperature with formation of precipitate. Thesample was refrigerated overnight and then worked up. The whiteprecipitate was filtered in vacuuo, washed with 2×10 ml hexane, anddried in the vacuum oven at ambient to afford 1.1 g of the methyl2-[2-((trans-1-(2-(2′,6′-difluorophenyl)cyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetateas a white solid, mpt. 81-88° C., as a 79:21 A:B (E:E,Z:E) isomer ratioin 51.9% isolated yield.

NMR (300 MHz ¹H CDCl3): 1.4 (t, 2H); 1.65-1.8 (d, 3H); 2.1 (m, 2H); 3.8(d, 3H), 4.0 (d, 3H); 5.0 (s, 2H); 6.8 (m, 2H), 7-7.2 (m, 2H); 7.3-7.5(m, 3H).

EXAMPLE 4 Preparation of E and Z imine isomers: (E,E) and (Z,E)-N-Methyl2-[2-((trans-1-(2-(2′,6′-difluorophenyl)cyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetamideCompounds 9.7A, 9.7B of Table 9

To a 25 ml reaction test tube under nitrogen atmosphere were charged0.95 g of (E,E:Z,E)-methyl2-[2-((trans-1-(2-(2′,6′-difluorophenyl)cyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetate(2.3 mmole) in 7 ml MeOH and 1.8 g 40% aqueous methyl amine (23 mmole)which was heated at 55-60 C. The reaction was monitored by TLC andworked up after 1.5 hours. Removed the methanol in vacuuo on the rotaryevaporator at 30° C. To the residue was added 125 ml ethyl acetate and50 ml water, partitioned, further washed the organic phase with 2×50 mlwater, dried over anhydrous MgSO₄, filtered, and concentrated in vacuuoon the rotary evaporator at 40° C. to give 1 g of (E,E:Z,E)-N-methyl2-[2-((trans-1-(2-(2′,6′-difluorophenyl)cyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetamideas a 76:24 A:B (E,E:Z,E) isomer ratio. This mixture was chromatographedon silica with 1:2 ethyl acetate:hexane to afford both (E,E) and (Z,E)isomers of the N-methyl2-[2-((trans-1-(2-(2′,6′difluorophenyl)cyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetamide.700 mg of isomer-A (E,E) was isolated as a clear oil and 150mg isomer B(Z,E) was isolated also as a pale yellow oil. The chromatrographedcombined isolated yield was 89.5%.

Compound 9.7A, Isomer A, E,E isomer: NMR (300 MHz ¹H CDCl3) 1.4 (t, 2H);1.8 (s, 3H); 2.1 (m, 2H); 2.9 (d, 3H); 3.9 (s, 3H); 4.9 (s, 2H); 6.7(bs, 1H); 6.8 (t, 2H); 7-7.2 (m, 2H); 7.3-7.5 (m, 3H).

Compound 9.7B, Isomer B, Z,E isomer NMR (300 MHz ¹H CDCl3) 1.3 (m, 1H);1.6 (m, 4H); 2.1 (m, 1H); 2.8 (m, 4H); 3.9 (s, 3H); 4.9 (s, 2H); 6.7(bs, 1H); 6.8 (t, 2H); 7-7.2 (m, 2H); 7.3-7.5 (m, 3H).

EXAMPLE 5 Preparation of Methyl2-[2-((1-(2-(4′-chlorophenol)-2-methylcyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetateCompound 2.14A of Table 2

Preparation of E and Z enone isomers of4-(4-chlorophenyl)-3-penten-2-one

To a 500 ml round bottom flask equipped with magnetic stirrer, nitrogeninlet and addition funnel were charged 10 g (0.065 moles) of4′-chloroacetophenone, 10.2 g (0.065 moles) ofethyl-trans-3-ethoxycrotonate, and 150 mls of dry dimethylformamide. Tothis solution was then added 7.3 g (0.065 moles) of potassium t-butoxidein one portion. The reaction was stirred at ambient temperature undernitrogen for a total of three days. The reaction mixture was then pouredinto 200 mls of water and the aqueous was extracted with 3×50 mls ofethyl ether to remove any unreacted starting material. The aqueousfraction was acidified to pH 2 with 1 N aqueous HCl, and extracted with3×100 mls of ethyl ether. The ether extract was washed with 2×100 mls ofwater and 100 mls of saturated sodium chloride solution, dried overanhydrous magnesium sulfate, filtered, and concentrated on a rotaryevaporator to afford 12.4 g of a tan solid. This solid was then stirredin 50 mls of conc. HCl for 2 hours at ambient temperature, then pouredinto 100 g of crushed ice, and extracted with 3×100 ml of ethyl ether.The ether extract was washed with 2×100 mls of water, 100 mls of brine,dried over anhydrous magnesium sulfate, filtered, and concentrated on arotary evaporator to afford 7.6 g of a yellow liquid,4-(4-chlorophenyl)-3-penten-2-one, which appeared to be a mixture of theE and Z enones, with some minor chemical impurities, in 59.3% crudeyield. The product was used in the next step without furtherpurification.

300 MHz ¹H NMR (tms=0 ppm) 2.3 (s, 3H); 2.5 (s, 3H); 6.5 (s, 1H);7.3-7.5 (m, 4H).

Preparation of trans andcis-1-(4-chlorophenyl)-1-methyl-2-acetylcyclopropane

To a 250 ml round bottom flask equipped with magnetic stirrer, nitrogeninlet and addition funnel were charged the trimethyl sulfoxonium iodide(8.5 g, 0.0386 moles), powdered sodium hydroxide (1.6 g, 0.0386 moles)and 100 mls of dry DMSO. The mixture was stirred at room temperature for1 hour, followed by the rapid addition of the(E>Z)-4-(4-chlorophenyl)-3-penten-2-one (7.5 g, 0.0386 moles)) in 10 mlsDMSO. The reaction was stirred for 3 days at ambient temperature, thenpoured into 200 mls of ice water and extracted with 3×100 ml of ethylether. The ether extract was washed with 2×100 mls of water, 100 mls ofbrine, dried over anhydrous MgSO₄, filtered through 2″ of silica gel,and concentrated on a rotary evaporator to afford 3.2 g of a thick paleyellow oil which was chromatographed on silica gel with 10% ethylacetate, 90% hexane. The pure fractions were combined and concentratedon the rotary evaporator to afford 1.4 g (17.2% isolated yield) of apale yellow liquid which was consistent with trans andcis-1-(4-chlorophenyl)-1-methyl-2-acetylcyclopropane upon analysis by300 Mz 1H NMR.

300 MHz ¹H NMR (tms=0 ppm) 1.2 (m, 1H); 1.4 (s, 3H); 1.6 (m, 1H); 2.2(m, 1H); 2.35 (s, 3H); 7.1-7.4 (m, 4H).

Preparation of Methyl2-[2-((1-(2-(4′-chlorophenyl)-2-methylcyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetate

To a 20 ml glass vial equipped with magnetic stirrer were charged the1.0 g (0.0048 moles) of the trans andcis-1-(4-chlorophenyl)-1-methyl-2-acetylcyclopropane, 1.2 g (0.0048moles) of the methyl (E)-2-(aminooxymethyl)phenyl glyoxylateO-methyloxime, and 10 mls of dry methanol. The vial was capped, andstirred overnight at ambient temperature. The reaction mixture was thenpoured into 100 mls of water and extracted with 3×100 ml of ethyl ether.The ether extract was washed with 2×100 mls of water, 100 mls of 1 NHCl, and 100 mls of saturated sodium chloride solution, dried overanhydrous MgSO₄, filtered, and concentrated on a rotary evaporator toafford 1.6 g of a thick orange oil which was chromatographed on silicagel with 20% ethyl acetate, 80% hexane. The pure fractions afterchromatography were combined and concentrated on a rotary evaporator toafford 0.75 g of a clear colorless viscous oil (36.5% isolated yield)which was consistent with isomer A, (E,E)-methyl2-[2-((1-(2-(4′-chlorophenyl)-2-methylcyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetateupon analysis by 300 MHz ¹H NMR with a 70:30 ratio of cyclopropaneisomers.

300 MHz ¹H NMR (tms=0 ppm) 1.15 (s, 3H) 1.2 (m, 1H); 1.4 (m, 1H); 1.6(m, 1H); 2.0(s, 3H); 3.85 (s, 3H); 4.0 (s, 3H); 5.0 (s, 2H); 7.1-7.3 (m,5H); 7.35-7.6 (m, 3H)

EXAMPLE 6 Preparation of (E,E)-N-Methyl2-[2-((1-(2-(4′-chlorophenyl)-2-methylcyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetamideCompound 3.14A of Table 3

To a 100 ml round bottom flask equipped with magnetic stirrer werecharged 0.7 g (0.00163 moles) of the (E,E)-methyl2-[2-((1-(2-(4′-dichlorophenyl)-2-methylcyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetate,25 mls of anhydrous methanol, and 1 ml (0.0129 moles) of 40% methylamine in water. The flask was stoppered, and stirred overnight atambient temperature. The reaction mixture was then poured into 100 mlsof water and extracted with 3×50 ml of ethyl ether. The ether extractwas washed with 2×50 mls of water, 50 mls of 1 N HCl, 50 mls ofsaturated sodium chloride solution, dried over anhydrous MgSO₄,filtered, and concentrated on a rotary evaporator to afford 0.7 g of ayellow viscous oil which was chromatographed on silica gel with 20%ethyl acetate, 80% hexane. The pure fractions were combined andconcentrated on a rotary evaporator to afford 0.55 g of a clearcolorless viscous oil (79% isolated yield) which was consistent withisomer A (E,E)-N-methyl2-[2-((1-(2-(4′-chlorophenyl)-2-methylcyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetamideupon analysis by 300 Mz ¹H NMR and as 70:30 mixture of cyclopropaneisomers

300 MHz ¹H NMR (tms=0 ppm) 1.15 (s, 3H) 1.2 (m, 1H); 1.4 (m, 1H); 1.65(m, 1H); 2.0(s, 3H); 2.9 (d, 3H); 4.0 (s, 3H); 5.0 (s, 2H); 6.8 (bs,1H); 7.1-7.3 (m, 5H); 7.35-7.6 (m, 3H).

EXAMPLE 7 Preparation of Methyl2-[2-((trans-1-(2-phenyl-2-methylcyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetateCompound 2.11 of Table 2

To a 25 ml reaction vial equipped with magnetic stirrer were charged217mg (1.25 mmole) of the trans-1-phenyl-1-methyl-2-acetylcyclopropaneand 298 mg (1.25 mmole) of the methyl (E)-2-(aminooxymethyl)phenylglyoxylate O-methyloxime in 5 ml of anhydrous methanol and 1 dropglacial acetic acid. The reaction was monitored by GC and after 3 hours90 mg more of the methyl 2-(bromomethyl)phenyl glyoxylate O-methyloximewas added and 5 drops of glacial acetic acid. After stirring 20 hours nomore starting material ketone remained and the reaction was worked up.The methanol was removed in vacuuo on the rotary evaporator. To theresidue was added 100 ml ethyl acetate and 50 ml water, partitioned,further washed the organic phase with 3×50 ml water, dried overanhydrous MgSO₄, filtered and concentrated in vacuuo on the rotaryevaporator to give 0.6 g of yellow oil with solid which waschromatographed on silica with 30:70 ethyl acetate:hexane. The purefractions were combined to afford 260 mg of a clear oil (isolated yield52.8%) whose NMR was consistent with methyl2-[2-((trans-1-(2-phenyl-2-methyl-cyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetateas a mixture of isomers, A>B.

NMR (300 MHz ¹H CDCl3): 1.1-1.4 (m, 5H); 1.75 (m, 1H); 2.0 (s, 3H); 3.85(s, 3H); 4.05 (s, 3H); 5.0 (s, 2H); 7.1-7.5 (m, 9H).

EXAMPLE 8 Preparation of (E,E and Z,E)-N-Methyl2-[2-((trans-1-(2-phenyl-2-methyl-cyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetamideCompound 3.11 of Table 3

To a 25 ml reaction test tube under nitrogen atmosphere were charged 160mg of the methyl2-[2-((trans-1-(2-phenyl-2-methyl-cyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetate(0.41 mmole) in 3 ml MeOH and 315 mg 40% aqueous methyl amine (4.1mmole) which was heated at 55-60 C. Monitored by TLC and worked up after1.5 hours. Removed the methanol in vacuuo on the rotary evaporator at 30C. To the residue was added 125 ml ethyl acetate and 50 ml water,partitioned, further washed the organic phase with 2×50 ml water, driedover anhydrous MgSO₄, filtered and concentrated in vacuuo on the rotaryevaporator at 40 C. to afford 130 mg (isolated yield 80.7%) of (E,E andZ,E)-N-methyl2-[2-((trans-1-(2-phenyl-2-methyl-cyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetamideas a clear oil in a 4:1 ratio of isomers A to B (E,E:Z,E).

NMR (300 MHz ¹H CDCl3): 1.1-1.4 (m, 5H); 1.75 (m, 1H); 1.95 (s, 3H); 2.9(d, 3H); 3.95 (s, 3H); 5.0 (s, 2H); 6.7 (bs, 1H); 7.1-7.5 (m, 9H).

Proton NMR data (300 MHz) are provided in Table 13 for typical examplesof Tables 1 to 12 and are illustrative of the present invention*

TABLE 13 Compd # NMR DATA 2.11 1.1-1.4 (m, 5H); 1.75 (m, 1H); 2.0 (s,3H); 3.85 (s, 3H); 4.05 (s, 3H); 5.0 (s, 2H); 7.1-7.5 (m, 9H). 2.14A1.15 (s, 3H) .1.2 (m, 1H); 1.4 (m, 1H); 1.6 (m, 1H); 2.0 (s, 3H); 3.85(s, 3H); 4.0 (s, 3H); 5.0 (s, 2H); 7.1-7.3 (m, 5H); 7.35-7.6 (m, 3H).3.11 1.1-1.4 (m, 5H); 1.75 (m, 1H); 1.95 (s, 3H); 2.9 (d, 3H); 3.95 (s,3H); 5.0 (s, 2H); 6.7 (bs, 1H); 7.1-7.5 (m, 9H). 3.14A 1.15 (s, 3H) 1.2(m, 1H); 1.4 (m, 1H); 1.65 (m, 1H); 2.0 (s, 3H); 2.9 (d, 3H); 4.0 (s,3H); 5.0 (s, 2H); 6.8 (bs, 1H); 7.1-7.3 (m, 5H); 7.35-7.6 (m, 3H). 8.11.3 (m, 1H); 1.7 (m, 1H); 1.85 (s, 3H); 1.95 (m, 1H); 2.2 (m, 1H); 3.85(s, 3H), 4.1 (s, 3H); 5.0 (s, 2H); 7.1 (m, 1H), 7.2 (m, 1H); 7.3 (d,2H); 7.4-7.6 (m, 3H). 8.1A 1.19-1.30 (1H, m), 1.50-1.58 (1H, m),1.75-1.85 (1H, m) 1.84 (3H, s), 2.06-2.14 (1H, m), 3.85 (3H, s), 4.05(3H, s), 4.98 (2H, s), 7.03-7.49 (7H, m). 8.1B 1.21-1.28 (1H, m),1.40-1.52 (1H, m), 1.70 (3H, s), 2.18-2.23 (1H, m) 2.61-2.70 (1H, m),3.80 (3H, s), 4.00 (3H, s), 4.97 (2H, s), 7.05-7.52 (7H, m). 8.7 1.4 (t,2H); 1.65-1.8 (d, 3H); 2.1 (m, 2H); 3.8 (d, 3H); 4.0 (d, 3H); 5.0 (s,2H); 6.8 (m, 2H), 7-7.2 (m, 2H); 7.3-7.5 (m, 3H). 9.1 1.2 (m, 1H); 1.6(m, 1H); 1.8 (s, 3H); 1.9 (m, 1H); 2.2 (m, 1H); 2.9 (d, 3H); 3.95 (s,3H), 5.0 (s, 2H); 6.7 (bs, 1H); 7.1 (m, 1H), 7.2 (m, 1H); 7.3 (d, 2H);7.4-7.6 (m, 3H). 9.1A 1.20-1.30 (1H, m), 1.51-1.58 (1H, m), 1.80-1.89(1H, m), 1.82 (3H, s), 2.2 (1H, m), 2.89 (3H, d), 3.96 (3H, s), 4.98(2H, s), 6.70 (1H, br), 7.05-7.48 (7H, m). 9.1B 1.22-1.30 (1H, m),1.40-1.51 (1H, m), 1.70 (3H, s), 2.15-2.23 (1H, m), 2.60-2.69 (1H,m),2.85 (3H, d), 3.90 (3H, s), 4.97 (2H, s), 6.70 (1H, br), 7.09-7.51 (7H,m). 9.7A 1.4 (t, 2H); 1.8 (s, 3H); 2.1 (m, 2H); 2.9 (d, 3H); 3.9 (s,3H); 4.9 (s, 2H); 6.7 (bs, 1H); 6.8 (t, 2H); 7-7.2 (m, 2H); 7.3-7.5 (m,3H). 9.7B 1.3 (m, 1H); 1.6 (m, 4H); 2.1 (m, 1H); 2.8 (m, 4H); 3.9 (s,3H); 4.9 (s, 2H); 6.7 (bs, 1H); 6.8 (t, 2H); 7-7.2 (m, 2H); 7.3-7.5 (m,3H). *NMR data for compounds designated by A or B are data for onesingle stereoisomer for R₂C═N—O. Compounds without designation are amixture of stereoisomers and the data provided is for the major isomer.

EXAMPLE 10

Numerous compounds of this invention were tested for fungicidal activityin vivo against the diseases described below. The compounds weredissolved in a 1:1 mixture of acetone and methanol 2:1:1 orN,N-dimethylformamide and diluted with a 2:1:1 mixture of water, acetoneand methanol (by volume) to achieve the appropriate concentration. Thesolution was sprayed onto the plants and allowed to dry for two hours.Then the plants were inoculated with fungal spores. Each test utilizedcontrol plants which were sprayed with the appropriate solvent andinoculated. For these protective tests, the plants were inoculated oneday after treating the plants with the compounds of this invention. Theremainder of the technique of each of the tests is given below alongwith the results for various compounds described herein by the Compound# against the various fungi at a dose of 150 grams per hectare. Theresults are percent disease control as compared to the untreated checkwherein one hundred was rated as complete disease control and zero as nodisease control. The application of the test fungal spores to the testplants was as follows:

Wheat Leaf Rust (WLR)

Puccinia recondita (f sp. tritici) was cultured on 7-day old wheat(cultivar Fielder) over a 12-day period in the greenhouse. Spores werecollected from the leaves by settling on aluminum foil. The spores werecleaned by sieving through a 250-micron opening screen and stored dry.The dried spores were used within one month. A spore suspension wasprepared from dry uredia by adding 20 mg (9.5 million spores) per ml ofSoltrol oil. The suspension was dispensed into gelatin capsules (0.7 mlcapacity) which attach to the oil atomizers. One capsule is used perflat of twenty 2-inch square pots of 7-day old plants, cultivar Fielder.After waiting for at least 15 minutes for the oil to evaporate from thewheat leaves, the plants were placed in a dark mist chamber (18-20° C.and 100% relative humidity) for 24 hours. The plants were then placed inthe greenhouse and evaluated after 12 days for disease.

Wheat Leaf Blotch (SNW)

Cultures of Septoria nodorum was maintained on Czapek-Dox V-8 juice agarplates in an incubator at 20° C. with alternating periods of 12 hours oflight and 12 hours of darkness for 2 weeks. A water suspension of thespores was obtained by shaking the portion of the plate with fungalmaterial in deionized water and filtering through cheesecloth. Thespore-containing water suspension was diluted to a spore concentrationof 3.0×10⁶ spores per ml. The inoculum was dispersed by a DeVilbissatomizer over one-week old Fielder wheat plants which had beenpreviously sprayed with the fungicide compound. The inoculated plantswere placed in a humidity cabinet at 20° C. with alternating 12 hours oflight and 12 hours of darkness for 7 days. The inoculated seedlings werethen moved to a controlled environment room at 20° C. for 2 days ofincubation. Disease control values were recorded as percent control.

Wheat Powdery Mildew (WPM)

Erysiphe graminis (f. sp. tritici) was cultured on wheat seedlings,cultivar Fielder, in a controlled temperature room at 18° C. Mildewspores were shaken from the culture plants onto 7-day old wheatseedlings which had been previously sprayed with the fungicide compound.The inoculated seedlings were kept in a controlled temperature room at18° C. and subirrigated. The percent disease control. was rated 7 daysafter the inoculation. Disease control values were recorded as percentcontrol.

Cucumber Powdery Mildew (CPM)

Sphaerotheca fulginea was maintained on cucumber plants, cultivar BushChampion, in the greenhouse. Inoculum was prepared by placing five toten heavily mildewed leaves in a glass jar with 500 ml of watercontaining 1 drop of Tween 80 (polyoxyethylene monooleate) per 100 ml.After shaking the liquid and leaves, the inoculum was filtered throughcheese cloth and misted onto the plants with a squirt bottle mister. Thespore count was 100,000 spores/ml. The plants were then placed in thegreenhouse for infection and incubation. The plants were scored sevendays after inoculation. Disease control values were recorded as percentcontrol.

Tomato Late Blight (TLB)

Cultures of Phytophthora infestans were maintained on green pea-amendedagar for two to three weeks. The spores were washed from the agar withwater and dispersed with a DeVilbiss atomizer over the leaves of 3-weekold Pixie tomato plants which had been previously treated with compoundof the present invention. The inoculated plants were placed in ahumidity cabinet at 20° C. for 24 hours for infection. The plants werethen removed to a controlled environment room at 20° C. and 90%humidity. The plants were scored for disease control after five days.

Grape Downy Mildew (GDM)

Plasmopara viticola was maintained leaves of grape plants, cultivarDelaware, in a controlled temperature chamber at 20° C. in humid airwith moderate light intensity for 7 to 8 days. A water suspension of thespores from infested leaves was obtained and the spore concentration wasadjusted to about 3×10⁵ per ml of water. Delaware grape plants wereinoculated by spraying the underside of leaves with a De Vilbissatomizer until small drops were observed on the leaves. The inoculatedplants were incubated in a mist chamber for 24 hours at 20° C. Theplants were then removed to a controlled environmental room at 20° C.Disease control values were recorded as percent control seven days afterinoculation.

Rice Blast (PB)

Cultures of Pyricularia oyrzae were maintained on potato dextrose agarfor two to three week. The spores were washed from the agar with watercontaining 1 drop of Tween 80 per 100 ml. After filtering the sporesuspension through two layers of cheese cloth, the spore count wasadjusted to 5×10⁵ per ml of water. The spore suspension was sprayed onto12-day old rice plants, cultivar M-1, using a DeVilbiss atomizer. Theinoculated plants were placed in a humidity at chamber 20° C. for 36hours to allow for infection. After the infection period the plants wereplaced in the greenhouse. After 6 days, the plants were scored fordisease control. Disease control values were recorded as percentcontrol.

Cucumber Downy Mildew (CDM)

Cucumber plants were maintained in the greenhouse. Large, fully expandedleaves were collected from the plates. The stems were wrapped withcotton, the leaves were placed in a large petri plate (15 cm. diameter)and the leaves were supported by glass rods. The upper cover of theplate was removed and the upper surface of the detached cucumber leafwas sprayed with the compounds of the present invention. The leaf wasallowed to dry in the air for approximately 2 hours. The cultures ofPseudoperonospora cubensis were maintained on cucumber plants. Afterextracting the spores by shaking the leaves in water, the lower surfaceof the treated cucumber leaves were sprayed with a spore concentrationof 100,000 spores per ml of water. The plates were returned to acontrolled environmental chamber at 20° C. and 90% humidity for fivedays. After this time, leaves were examined for disease development.Disease control values were recorded as percent control.

Cucumber Anthracnose (CA)

The fungal pathogen Colletotrichum lagenarium was cultured on potatodextrose agar (PDA) in the dark at 22 C. for a period of 8 to 14 days.Spores of C. lagenarium were removed from the PDA plates by flooding theplate surface with distilled water, amended with 0.5% v/w of yeastextract. The upper surface of the fungal colony was scraped with a bluntinstrument until most of the spores were released into the aqueousenvironment. The spore suspension was filtered though cheesecloth, andthe spore count was adjusted by adding more water, containing the yeastextract, until 3.0×10⁶ spores per ml of water was achieved.

The chemically-treated cucumber plants were 15-days old, cultivar BushChampion. The upper leaf surface of the plants were sprayed with thespore suspension until runoff, using a hand-held pump spray bottle. Theplants were placed in a fluorescent-lighted mist chamber (12 hr light,12 hr dark) for 48 hours. After that infection period, the plants wereplaced in a growth chamber for 3 days at 25 C. and 90% humidity. Thetreated plants were then evaluated for disease control. Disease controlvalues were recorded as percent control.

When tested against wheat leaf rust at 150 grams per hectare compounds3.11, 3.14A, 9.1, and 9.7A exhibited 100% control.

When tested against wheat leaf blotch at 150 grams per hectare compounds3.11, 3.14A, 9.1, 9.7A, and 9.8 exhibited 90% or better control.

When tested against wheat powdery mildew at 150 grams per hectarecompounds 9.1, and 9.7A exhibited 90% or better control.

When tested against cucumber powdery mildew at a dose of 150 grams perhectare compounds 3.11, 3.14A, 8.1, 9.1, and 9.7A exhibited 100%control.

When tested against tomato late blight at 150 grams per hectarecompounds 3.11, 3.14A, 8.1, 9.1, 9.7A, and 9.8 exhibited 95% or bettercontrol.

When tested against grape downy mildew at 150 grams per hectarecompounds 9.1, and 9.7A exhibited 100% or better control.

When tested against rice blast at 150 grams per hectare compounds 3.11,3.14A, 8.1, 9.1, and 9.7A exhibited 95% or better control.

When tested against cucumber downy mildew at 150 grams per hectarecompounds 3.11, 3.14A, 9.1, and 9.8 and exhibited 95% or better controland when tested at 9 grams per hectare compound 9.7A exhibited 100%control.

When tested against cucumber anthracnose at 150 grams per hectarecompounds 3.11, 3.14A, 9.1, 9.7A and 9.8 exhibited 100% control.

The compounds of this invention are useful as agricultural fungicidesand, as such, can be applied to various loci such as the seed, the soilor the foliage of plants to be protected.

The compounds of this invention can be applied as fungicidal sprays bymethods commonly employed, such as conventional high-volume hydraulicsprays, low-volume sprays, air-blast spray, aerial sprays and dusts. Thedilution and rate of application will depend upon the type of equipmentemployed, the method of application, plants to be treated and diseasesto be controlled. Generally, the compounds of this invention will beapplied in amount of from about 0.005 kilogram to about 50 kilograms perhectare and preferably from about 0.025 to about 25 kilograms perhectare of the active ingredient.

As a seed protectant, the amount of toxicant coated on the seed isusually at a dosage rate of from about 0.05 to about 20, preferably fromabout 0.05 to about 4, and more preferably from about 0.1 to about 1grams per hundred kilograms of seed. As a soil fungicide the chemicalcan be incorporated in the soil or applied to the surface usually at arate of from about 0.02 to about 20, preferably from about 0.05 to about10, and more preferably from about 0.1 to about 5 kilograms per hectare.As a foliar fungicide, the toxicant is usually applied to growing plantsat a rate of from about 0.01 to about 10, preferably from about 0.02 to5, and more preferably from about 0.25 to about 1 kilograms per hectare.

Inasmuch as the compounds of this invention display fungicidal activity,these compounds can be combined with other known fungicides to providebroad spectrum activity. Suitable fungicides include, but are notlimited to, those compounds listed in U.S. Pat. No. 5,252,594 (see inparticular columns 14 and 15). Other known fungicides which an becombined with the compounds of this invention are dimethomorph,cymoxanil, thifluzamide, furalaxyl, ofurace, benalaxyl, oxadixyl,propamocarb, cyprofuram, fenpiclonil, fludioxonil, pyrimethanil,cyprodinil, triticonazole, fluquinconazole, metconazole, spiroxamine,carpropamid, azoxystrobin, kresoxim-methyl, metominostrobin andtrifloxystrobin.

The compounds of this invention can be advantageously employed invarious ways. Since these compounds possess broad spectrum fungicidalactivity, they can be employed in the storage of cereal grain. Thesecompounds can also be employed as fungicides in cereals including wheat,barley and rye, in rice, peanuts, beans and grapes, on turf, in fruit,nut and vegetable orchards, and for golf course applications.

Examples of diseases against which the compounds of the invention areuseful include helminthosporium of corn and barley, wheat and barleypowdery mildew, wheat leaf and stem rusts, barley stripe and leaf rust,tomato early blight, tomato late blight, peanut early leaf spot, grapepowdery mildew, grape black rot, apple scab, apple powdery mildew,cucumber powdery mildew, brown rot of fruits, botrytis, bean powderymildew, cucumber anthracnose, wheat septoria nodorum, rice sheath blightand rice blast.

Compositions and formulations according to the present invention mayalso include known pesticidal compounds. This expands the spectrum ofactivity of the preparation and may give rise to synergism. Suitableinsecticides known in the art include those listed in U.S. Pat. No.5,075,471, see in particular columns 14 and 15.

The compounds of the present invention can be used in the form ofcompositions or formulations. Examples of the preparation ofcompositions and formulations can be found in the American ChemicalSociety publication “Pesticidal Formulation Research,” (1969), Advancesin Chemistry Series No. 86, written by Wade Van Valkenburg; and theMarcel Dekker, Inc. publication “Pesticide Formulations”, (1973) editedby Wade Van Valkenburg. In these compositions and formulations, theactive substance is mixed with conventional inert agronomicallyacceptable (i.e., plant compatible and/or pesticidally inert) pesticidediluents or extenders such as solid carrier material or liquid carriermaterial, of the type usable in conventional pesticide compositions orformulations. By “agronomically acceptable carrier” is meant anysubstance which can be used to dissolve, disperse of diffuse the activeingredient in the composition without impairing the active ingredient'seffectiveness and which by itself has no significant detrimental effecton the soil, equipment, desirable plants, or agronomic environment. Ifdesired, adjuvants such as surfactants, stabilizers, antifoam agents andanti-drift agents may also be combined.

Examples of compositions and formulations according to the invention areaqueous solutions and dispersions, oily solutions and oil dispersions,pastes, dusting powders, wettable powders, emulsifiable concentrates,flowables, granules, baits, invert emulsions, aerosol compositions andfumigating candles. Wettable powders, pastes, flowables and emulsifiableconcentrates are concentrated preparations which are diluted with waterbefore or during use. In such formulations, the compounds are extendedwith a liquid or solid carrier and, when desired, suitable surfactantsare incorporated. Baits are preparations generally comprising a food orother substance attractive to insects, that includes at least onecompound of the instant invention.

It is usually desirable, particularly in the case of foliar sprayformulations, to include adjuvants, such as wetting agents, spreadingagents, dispersing agents, stickers, adhesive and the like in accordancewith agricultural practices. A listing of such adjuvants commonly usedin the art, and a discussion of adjuvants, can be found in manyreferences, such as in the John W. McCutcheon, Inc. publication“Detergents and Emulsifiers, Annual.”

The active compounds of the present invention may be employed alone orin the form of mixtures with one another and/or with such solid and/orliquid dispersible carrier vehicles and/or with other known compatibleactive agents, especially plant protection agents, such as otherinsecticides, arthropodicides, nematicides, fungicides, bactericides,rodenticides, herbicides, fertilizers, growth-regulating agents,synergists.

In the compositions of the invention, the active compound is present inan amount substantially between about 0.0001 (1:999,999)−99 (99:1) % byweight. For compositions suitable for storage or transportation, theamount of active ingredient is preferably between about 0.5 (1:199)−90(9:1) % by weight, and more preferably between about 1 (1:99)−75 (3:1) %by weight of the mixture. Compositions suitable for direct applicationor field application generally contain the active compound in an amountsubstantially between about 0.0001 (1:999,999)−95 (19:1) %, preferablybetween about 0.0005 (1:199,999)−90 (9:1) % by weight, and morepreferably between about 0.001 (1:99,999)−75 (3:1) % by weight of themixture. The composition can also be stated as a ratio of the compoundto the carrier. In the present invention the weight ratio of thesematerials (active compound/carrier) can vary from 99:1 (99%) to 1:4(20%) and more preferably from 10:1 (91%) to 1:3 (25%).

In general, the compounds of this invention can be dissolved in certainsolvents such as acetone, methanol, ethanol, dimethylformamide, pyridineor dimethyl sulfoxide and such solutions can be diluted with water. Theconcentrations of the solution can vary from about 1% to about 90% witha preferred range being from about 5% to about 50%.

For the preparation of emulsifiable concentrates, the compound can bedissolved in suitable organic solvents, or a mixture of solvents,together with an emulsifying agent to enhance dispersion of the compoundin water. The concentration of the active ingredient in emulsifiableconcentrates is usually from about 10% to about 90%, and in flowableemulsion concentrates, can be as high as about 75%.

Wettable powders suitable for spraying, can be prepared by admixing thecompound with a finely divided solid, such as clay, inorganic silicateand carbonate, and silica and incorporating wetting agents, stickingagents, and/or dispersing agents in such mixtures. The concentration ofactive ingredients in such formulations is usually in the range of fromabout 20% to about 99%, preferably from about 40% to about 75%. Atypical wettable powder is made by blending 50 parts of a compound ofFormula I, 45 parts of a synthetic precipitated hydrated silicon dioxideand 5 parts of sodium lignosulfonate. In another preparation a kaolintype (Barden) clay is used in place of the synthetic precipitatedhydrated silicon dioxide in the above wettable powder, and in anothersuch preparation 25% of the silicon dioxide is replaced with a syntheticsodium silicoaluminate.

Dusts are prepared by mixing compounds of Formula I, or theenantiomorphs, salts and complexes thereof with finely divided inertsolids which can be organic or inorganic in nature. Materials useful forthis purpose include botanical flours, silicas, silicates, carbonatesand clays. One convenient method of preparing a dust is to dilute awettable powder with a finely divided carrier. Dust concentratescontaining from about 20% to about 80% of the active ingredient arecommonly made and are subsequently diluted to from about 1% to about 10%use concentration.

In addition to the aforementioned ingredients the preparations accordingto the invention may also contain other substances commonly used inpreparations of this kind. For example, a lubricant, such as calciumstearate or magnesium stearate, may be added to a wettable powder or toa mixture to be granulated. Furthermore there may, for example, be added“adhesives” such as polyvinylalcohol-cellulose derivatives or othercolloidal materials, such as casein, to improve the adherence of thepesticide to the surface to be protected.

We claim:
 1. A compound of the formula:

wherein X is N or CH; Z is O, S, or NR₈; A is hydrogen, halo, cyano,(C₁-C₁₂)alkyl, or (C₁-C₁₂)alkoxy; R₁ and R₈ are independently hydrogenor (C₁-C₄)alkyl; R₂ is hydrogen, (C₁-C₁₂)alkyl, halo(C₁-C₁₂)alkyl,(C₃-C₇)cycloalkyl, halo(C₃-C₇)cycloalkyl, (C₂-C₈)alkenyl,halo(C₂-C₈)alkenyl, (C₂-C₈)alkynyl, halo(C₂-C₈)alkynyl, or cyano; R₃ ishydrogen, (C₁-C₁₂)alkyl, halo(C₁-C₁₂)alkyl, (C₃-C₇)cycloalkyl,halo(C₃-C₇)cycloalkyl, (C₂-C₈)alkenyl, halo(C₂-C₈)alkenyl,(C₂-C₈)alkynyl, or halo(C₂-C₈)alkynyl; R₄ and R₅ are independentlyhydrogen, (C₁-C₁₂)alkyl, halo(C₁-C₁₂)alkyl, (C₃-C₇)cycloalkyl,halo(C₃-C₇)cycloalkyl, (C₂-C₈)alkenyl, halo(C₂-C₈)alkenyl,(C₂-C₈)alkynyl, halo(C₂-C₈)alkynyl, halo, cyano, or(C₁-C₄)alkoxycarbonyl; and wherein A) R₇ is aryl, arylalkyl,heterocyclic or heterocyclic(C₁-C₄)alkyl wherein the aryl orheterocyclic ring is substituted with from 2 to 5 substituents andwherein the positions on the aryl and heterocyclic rings adjacent to thebond to the cyclopropyl ring are both substituted and R₆ is hydrogen,(C₁-C₁₂)alkyl, halo(C₁-C₁₂)alkyl, (C₃-C₇)cycloalkyl,halo(C₃-C₇)cycloalkyl, (C₂-C₈)alkenyl, halo(C₂-C₈)alkenyl,(C₂-C₈)alkynyl, or halo(C₂-C₈)alkynyl; or B) R₇ is aryl, arylalkyl,heterocyclic or heterocyclic(C₁-C₄)alkyl wherein the aryl orheterocyclic ring is unsubstituted or substituted from 1 to 4substituents wherein at least one of the positions on the aryl orheterocyclic rings adjacent to the bond to the cyclopropyl ring is ahydrogen and R₆ is selected from the group consisting of (C₁-C₁₂)alkyl,halo(C₁-C₁₂)alkyl, (C₃-C₇)cycloalkyl, halo(C₃-C₇)cycloalkyl,(C₂-C₈)alkenyl, halo(C₂-C₈)alkenyl, (C₂-C₈)alkynyl, orhalo(C₂-C₈)alkynyl; and their salts, complexes, enantiomorphs, andstereoisomers; and mixtures thereof.
 2. The compound of claim 1 whereinX is CH, Z is O, R₂ is (C₁-C₁₂)alkyl, and R₃ is H.
 3. The compound ofclaim 2 wherein R₇ is 2,6-dichlorophenyl, 2,6-difluorophenyl,2,6-dibromophenyl, 2,6-bis(trifluoromethyl)phenyl,2,3,6-trichlorophenyl, 2,3,6-trifluorophenyl, 2,3,6-tribromophenyl,2,3,6-tris(trifluoromethyl)phenyl, 2,4,6-trichlorophenyl,2,4,6-trifluorophenyl, 2,4,6-tribromophenyl, or2,4,6-tris(trifluoromethyl)phenyl.
 4. The compound of claim 1 wherein Xis N, Z is O or NH, R₂ is (C₁-C₁₂)alkyl and R₃ is H.
 5. The compound ofclaim 4 wherein R₇ is 2,6-dichlorophenyl, 2,6-difluorophenyl,2,6-dibromophenyl, 2,6-bis(trifluoromethyl)phenyl,2,3,6-trichlorophenyl, 2,3,6-trifluorophenyl, 2,3,6-tribromophenyl,2,3,6-tris(trifluoromethyl)phenyl, 2,4,6-trichlorophenyl,2,4,6-trifluorophenyl, 2,4,6-tribromophenyl, or2,4,6-tris(trifluoromethyl)phenyl.
 6. The compound of claim 1 where thecompound isN-methyl-2-[2-((trans-1-(2-(2′,6′-dichloromethylphenyl)cyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetamide.7. The compound of claim 2 wherein R₆ is (C₁-C₁₂)alkyl and R₇ is phenyl,2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 4-fluorophenyl,4-bromophenyl, 2-(trifluoromethyl)phenyl, 2,4-dichlorophenyl,2,4-diifluorophenyl, 2,4-dibromophenyl, or2,4-bis(trifluoromethyl)phenyl.
 8. The compound of claim 4 wherein R₆ is(C₁-C₁₂)alkyl and R₇ is phenyl, 2-chlorophenyl, 3-chlorophenyl,4-chlorophenyl, 4-fluorophenyl, 4-bromophenyl,2-(trifluoromethyl)phenyl, 2,4-dichlorophenyl, 2,4-diifluorophenyl,2,4-dibromophenyl, or 2,4-bis(trifluoromethyl)phenyl.
 9. The compound ofclaim 1 where the compound is N-methyl2-[2-((trans-1-(2-phenyl-2-methylcyclopropyl)ethylidene)aminooxymethyl)phenyl]-2-methoxyiminoacetamide.10. A method of preparation of the compounds of claim 4 wherein X is N,Z is O, and R₆ is (C₁-C₁₂)alkyl comprising the step of reacting methyl(E)-2-(aminooxymethyl)phenyl glyoxylate O-methyloxime with a 1-aryl or1-heteroaryl-1-(C₁-C₁₂)alkyl-2-((C═O)(C₁-C₁₂)alkyl)cyclopropane.
 11. Afungicidal composition for controlling phytopathogenic fungi whichcomprises an agronomically acceptable carrier and the compound of claim1 wherein the ratio of the carrier to the compound is between 99:1 and1:4.
 12. A method for controlling phytopathogenic fungi which comprisesapplying the compound of claim 1 to the locus where control is desired,at a rate of from 0.005 to 50 kilograms per hectare.